Marya Ahmed
California Institute of Technology, Chemical Engineering, Department Member
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Research Interests: Engineering, Chemical Engineering, Materials Science, Nanoparticle, Medicine, and 15 moreGene expression, Biological Sciences, DNA, Polymer, Humans, Magnetic nanoparticles, Cationic polymerization, Dynamic Light Scattering, Iron Oxide Nanoparticles, Gene Delivery, Magnetic Nanoparticles, Coprecipitation, Cations, Drug Carriers, and Magnetite Nanoparticles
Abstract In this paper, a novel low-temperature 3 D printing technique is introduced and characterized through a parametric printability study to fabricate poly-lactic-co-glycolic acid (PLGA) constructs using methyl ethyl ketone (MEK) as... more
Abstract In this paper, a novel low-temperature 3 D printing technique is introduced and characterized through a parametric printability study to fabricate poly-lactic-co-glycolic acid (PLGA) constructs using methyl ethyl ketone (MEK) as a solvent. The effects of varying concentrations of PLGA in MEK solvent, lactic to glycolic ratio of PLGA, the molecular weight of PLGA, and the scaling of PLGA constructs on the printability are investigated. PLGA concentrations of higher than 80% w/v, lactic to glycolic ratio more than 75%, molecular weight more than 100 kDa, and printing through nozzles smaller than 0.96 mm internal diameter are recommended for 3 D printing of PLGA constructs with high shape fidelity. Ultimately, a vacuum drying solvent removal process is implemented, and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy is used to confirm complete removal of the solvent from PLGA constructs. The results of this study can be used for the development of drug-eluting implants.
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Raw honey naturally possesses a number of health benefits that are imbued by its components, including phenolics acids, flavonoids, enzymes, sugars, and organic acids. Processing of raw honey at high temperatures, often leads to a loss of... more
Raw honey naturally possesses a number of health benefits that are imbued by its components, including phenolics acids, flavonoids, enzymes, sugars, and organic acids. Processing of raw honey at high temperatures, often leads to a loss of biological activity and active ingredients, hence, reducing the medicinal benefits of processed honey samples. This study describes that the processing of raw honey into honey-based candies slightly changed the physicochemical properties of raw honey, as was observed by the loss of diastase activity and reduction in hydrogen peroxide content in honey-based candies. However, the overall health benefits of honey-based candies were maintained. The processing of honey into candies (lozenges and drops) maintained antibacterial and anti-inflammatory activities of honey candies relative to the raw honey samples.
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Gold nanoparticles (GNPs) are well-documented for their size and surface chemistry–dependent electronic and optical properties that are extensively utilized to develop highly sensitive immunoassays. GNP-based immuno-polymerase chain... more
Gold nanoparticles (GNPs) are well-documented for their size and surface chemistry–dependent electronic and optical properties that are extensively utilized to develop highly sensitive immunoassays. GNP-based immuno-polymerase chain reaction (immuno-PCR) is especially interesting due to the facile loading of biomolecules on the surface of GNP probes and has been utilized to develop analyte-specific assays. In this study, the role of size and surface chemistry of GNPs is explored in detail to develop a highly sensitive and reproducible immuno-PCR assay for specific detection of biotinylated analytes. Our results indicate that smaller-sized gold nanoparticles outperform the larger ones in terms of their sensitivity in immuno-PCR assay and show superior loading of proteins and oligonucleotides on the surface of nanoparticles. Furthermore, the role of different macromolecular stabilizers (such as polyethylene glycol (PEG), bovine serum albumin (BSA), and PEGylated BSA) was compared to optimize the loading of biomolecules and to improve the signal-to-noise ratio of GNP probes. mPEG-BSA-functionalized GNP probes of 15 nm were found to be highly sensitive at low concentrations of analytes and significantly (~ 30 fold) improve the limit of detection of analytes in comparison with ELISA assay.
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Radiative energy fuelled water harvesting hydrogels.
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Calcium mediated complexation of siRNA with phosphorylcholine based polymers for efficient gene knockdown in HeLa cells in the presence and absence of serum.
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Research Interests: Biochemistry, Genetics, Biophysics, Chemistry, Biotechnology, and 15 moreCancer, Cell Biology, Cytotoxicity, Gold, Bioconjugate Chemistry, Cancer Cell Lines, Cancer cells, CARBOHYDRATES, Antitumor Activity, Human Fibroblasts, Conjugate, Anticancer Compounds, Antineoplastic Agents, Biochemistry and cell biology, and fibroblasts
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Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment... more
Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed by combining current cancer therapies with nanotechnology. The applications of nanotherapeutics for both primary and metastatic BC treatments are developing rapidly, and new ideas and technologies are being discovered. Several recent reviews covered the advancement of nanotherapeutics for primary BC, while also discussing certain aspects of treatments for metastatic BC. This review provides comp...
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A wide variety of polymers have found a range of applications as biomaterials in clinical medicine, due to their versatile structure and properties. Polymeric biomaterials can be derived from natural or synthetic polymers, and can be... more
A wide variety of polymers have found a range of applications as biomaterials in clinical medicine, due to their versatile structure and properties. Polymeric biomaterials can be derived from natural or synthetic polymers, and can be biodegradable or non-biodegradable, depending on their applications which can include biomedical implants, either as bulk materials or as implant coatings, as well as nanocarriers for drug and gene delivery. This chapter provides an overview of the history and development of polymeric biomaterials in specific fields of medicine. Some current researches into novel approaches toward polymeric medicine are also discussed.
This study involves the design and development of disulfide bridge-linked antimicrobial peptides using the host defense protein Angiogenin 4 (chAng4) as a template. The mini peptides derived from chAng4 (mCA4s) were evaluated for their... more
This study involves the design and development of disulfide bridge-linked antimicrobial peptides using the host defense protein Angiogenin 4 (chAng4) as a template. The mini peptides derived from chAng4 (mCA4s) were evaluated for their antibacterial efficacies in various pathogenic bacterial strains, and the role of the oxidation state of thiols in the peptide sequence and its implication on antibacterial properties were explored. A remarkable property of these synthetic mCA4 peptides is their capability to flocculate bacteria and mediate bacterial-specific killing, in the absence of any other external stimulus. mCA4s were further evaluated for their cellular uptake, hemolytic activities, toxicities, and immunomodulatory activities in different eukaryotic cell lines. The results indicate that disulfide bridge-containing cationic amphipathic peptides show superior antibacterial efficacies, are nontoxic and nonhemolytic, and mediate bacterial flocculation and killing, in the absence o...
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In this study, we report that host defense protein-derived ten amino acid long disulfide-linked peptides self-assemble in the form of β-sheets and β-turns, and exhibit concentration-dependent self-assembly in the form...
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The concept of dual drug delivery to treat relapsing tumors is a well-studied approach to improve the antitumor efficacies and to reduce the side effects of single drug chemotherapeutic treatments. One of the major issues with dual drug... more
The concept of dual drug delivery to treat relapsing tumors is a well-studied approach to improve the antitumor efficacies and to reduce the side effects of single drug chemotherapeutic treatments. One of the major issues with dual drug delivery to treat drug resistant tumors is the concentration and ratio dependent antagonistic behavior of two drugs, which may reverse the anticancer efficacies of individual chemotherapeutics and stimulate the growth of tumor cells. In this paper, we address this issue by developing diatomaceous earth embedded core shell materials, which are capable of encapsulating two chemotherapeutic drugs at constant molar ratios, in different compartments of a single drug delivery carrier. The encapsulation of each drug in different compartments of delivery carrier (core of diatoms versus shell of cyclodextrin) then controls the release rate of both drugs in situ, and maintains the optimal molar ratios required for their synergistic outcomes in vitro.
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The exponential increase in heavy metal usage for industrial applications has led to the limited supply of clean water for human needs. Iron is one of the examples of heavy metals, which is responsible for an unpleasant taste of water and... more
The exponential increase in heavy metal usage for industrial applications has led to the limited supply of clean water for human needs. Iron is one of the examples of heavy metals, which is responsible for an unpleasant taste of water and its discoloration, and is also associated with elevated health risks if it persists in drinking water for a prolonged period of time. The adsorption of a soluble form of iron (Fe2+) from water resources is generally accomplished in the presence of natural or synthetic polymers or nanoparticles, followed by their filtration from treated water. The self-assembly of these colloidal carriers into macroarchitectures can help in achieving the facile removal of metal-chelated materials from treated water and hence can reduce the cost and improve the efficiency of the water purification process. In this study, we aim to develop a facile one-pot strategy for the synthesis of polymeric composites with embedded nanocrystalline cellulose (NCC) for the chelatio...
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Water recycling efficacies of B5AMA hydrogels at ambient temperature.
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Quinolones and fluoroquinolones are widely used antibacterial agents. Nalidixic acid (NA) is a first-generation quinolone-based antibiotic that has a narrow spectrum and poor pharmacokinetics. Here, we describe a family of... more
Quinolones and fluoroquinolones are widely used antibacterial agents. Nalidixic acid (NA) is a first-generation quinolone-based antibiotic that has a narrow spectrum and poor pharmacokinetics. Here, we describe a family of peptide-nalidixic acid conjugates featuring different levels of hydrophobicity and molecular charge prepared by solid-phase peptide synthesis that exhibit intriguing improvements in potency. In comparison to NA, which has a low level of potency in S. aureus, the NA peptide conjugates with optimized hydrophobicities and molecular charges exhibited significantly improved antibacterial activity. The most potent NA conjugate-featuring a peptide containing cyclohexylalanine and arginine-exhibited efficient bacterial uptake and, notably, specific inhibition of S. aureus DNA gyrase. A systematic study of peptide-NA conjugates revealed that a fine balance of cationic charge and hydrophobicity in an appendage anchored to the core of the drug is required to overcome the int...
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Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or... more
Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delive...
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Mitochondria are organelles with critical roles in key processes within eukaryotic cells, and their dysfunction is linked with numerous diseases including neurodegenerative disorders and cancer. Pharmacological manipulation of... more
Mitochondria are organelles with critical roles in key processes within eukaryotic cells, and their dysfunction is linked with numerous diseases including neurodegenerative disorders and cancer. Pharmacological manipulation of mitochondrial function is therefore important both for basic science research and eventually, clinical medicine. However, in comparison to other organelles, mitochondria are difficult to access due to their hydrophobic and dense double membrane system as well as their negative membrane potential. To tackle the challenge of targeting these important subcellular compartments, significant effort has been put forward to develop mitochondria-targeted systems capable of transporting bioactive cargo into the mitochondrial interior. Systems now exist that utilize small molecule, peptide, liposome, and nanoparticle-based transport. The vectors available vary in size and structure and can facilitate transport of a variety of compounds for mitochondrial delivery. Notably...
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Nanogels are prominent examples of "smart" nanomaterials, which are designed to incorporate biologically relevant (macro)molecules for systemic delivery. Although these systems are carefully engineered, only a handful of studies... more
Nanogels are prominent examples of "smart" nanomaterials, which are designed to incorporate biologically relevant (macro)molecules for systemic delivery. Although these systems are carefully engineered, only a handful of studies discuss the blood compatibility of nanogels, and no systematic studies are available on how the presence of net or surface charges impacts the hemocompatibility of these nanomaterials. Therefore, in this study, temperature responsive, galactose based nanogels bearing net positive, negative, or neutral charges, either in the core or shell of nanogels, are prepared and are subsequently evaluated for their blood compatibility profiles. The nanogels containing neutral core and shell, cationic core with neutral shell, anionic core with neutral shell, neutral core with cationic shell, and neutral core with anionic shell are prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization approach. The evaluation of complement activation...
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The insult to liver by toxic materials leads to cirrhosis, hepatitis and cancer. Upon administration, drugs accumulate in liver, which is systemically cleared by reticuloendothelial system. However, specific targeting of drugs to liver is... more
The insult to liver by toxic materials leads to cirrhosis, hepatitis and cancer. Upon administration, drugs accumulate in liver, which is systemically cleared by reticuloendothelial system. However, specific targeting of drugs to liver is a serious challenge. Specific delivery of molecules to hepatocytes is accomplished by targeting cell surface lectins, asialoglycoprotein receptors. Asialofetuin, N-acetyl glucosamine and galactose are high-affinity ligands of asialoglycoprotein receptors. The bioconjugation of drugs, fluorescent molecules and gene delivery vectors with lectin-targeting agents, and their delivery in liver hepatocytes, is discussed. Mannose and N-acetyl glucosamine conjugates are evaluated for their delivery to hepatic stellate and kupffer cells. The glycosylated gene and drug delivery vectors in clinical trials are outlined.
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A large number of cationic polymers has been prepared and studied for their gene delivery efficacies, since the failure of retro-virus vector-based gene therapy trials in the 2000s. The introduction of the living radical polymerization... more
A large number of cationic polymers has been prepared and studied for their gene delivery efficacies, since the failure of retro-virus vector-based gene therapy trials in the 2000s. The introduction of the living radical polymerization (LRP) approach has allowed the synthesis of tailored gene delivery vectors of known molecular weights, architectures and compositions for gene delivery applications. The term “gene delivery” refers to the delivery of both deoxyribonucleic acid (DNA) and small interfering ribonucleic acid (siRNA) in living cells and tissues. Although the cargo delivery site for the two nucleic acids is different, the basic components of cationic vectors exploited in the design of gene delivery vectors are essentially the same. For LRP, atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer polymerization (RAFT) have allowed the synthesis of cationic vectors of near precise dimensions, hence establishing structure–activity relationships between cationic vectors and their gene delivery profiles. This attribute of LRP has enabled researchers to pinpoint and overcome the hurdles associated with traditional cationic polymers for gene delivery applications. In this chapter a brief account of the types of cationic vectors prepared by LRP and their role in gene expression in vitro and in vivo is discussed.
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Antibody-dependent cellular cytotoxicity (ADCC) is a cytolytic mechanism that can elicit in vivo antitumor effects and can play a significant role in the efficacy of antibody treatments for cancer. Here, we prepared cetuximab,... more
Antibody-dependent cellular cytotoxicity (ADCC) is a cytolytic mechanism that can elicit in vivo antitumor effects and can play a significant role in the efficacy of antibody treatments for cancer. Here, we prepared cetuximab, panitumumab, and rituximab containing gold nanoparticles and investigated their ability to produce an ADCC effect in vivo. Cetuximab treatment of EGFR-expressing H1975 tumor xenografts showed significant tumor regression due to the ADCC activity of the antibody in vivo, while the control antibody, panitumumab, did not. However, all three antibody containing nanoparticles are not able to suppress tumor growth in the same in vivo mouse model. The antibody containing nanoparticles localized in the tumors and did not suppress the immune function of the animals, so the lack of tumor growth suppression of the cetuximab containing nanoparticle suggests that immobilizing antibodies onto a nanoparticle significantly decreases the ability of the antibody to promote an A...
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ABSTRACT The review provides a comprehensive account on the development of gene delivery vectors via reversible addition-fragmentation chain transfer polymerization (RAFT) approach. Since the development and use of the first non-viral... more
ABSTRACT The review provides a comprehensive account on the development of gene delivery vectors via reversible addition-fragmentation chain transfer polymerization (RAFT) approach. Since the development and use of the first non-viral vector for gene delivery applications, a wide range of polymers were synthesized and studied for their gene delivery efficacies. With the advent of living radical polymerization (LRP), well-defined polymers with varying molecular weights, compositions and architectures were synthesized to evaluate their potency as gene delivery vectors. Atom transfer radical polymerization (ATRP) and RAFT are two widely used LRP approaches for gene delivery applications. This review focuses primarily on the synthesis and use of cationic polymers via RAFT for DNA and siRNA delivery in vitro and in vivo. RAFT polymerization has allowed the facile synthesis of tailor-made cationic polymers with pendent biocompatible moieties which are promising non-viral gene delivery vectors. Advanced structure–activity relationship studies between the polymers and gene expression have been possible due to the remarkable control in the design of these polymers via the RAFT process. As a result, biocompatible and non-toxic polymers are produced under aqueous conditions and are identified as potent gene delivery vectors in vitro and in vivo. Polymeric functionalized nanomaterials were produced and studied for gene delivery applications. The consistency of results obtained from different research groups and identification of improved gene expression efficacies of RAFT based gene delivery vectors indicate the scope of this polymerization approach for future studies.
Research Interests: Engineering, DNA, CS, AFM, ATRP, and 11 morePll, CHEMICAL SCIENCES, Gene Delivery, PEG, Snp, siRNA, Structure activity Relationship, DLS, GFP, PSMA, and Raft
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ABSTRACT The review provides a comprehensive account on the development of gene delivery vectors via reversible addition-fragmentation chain transfer polymerization (RAFT) approach. Since the development and use of the first non-viral... more
ABSTRACT The review provides a comprehensive account on the development of gene delivery vectors via reversible addition-fragmentation chain transfer polymerization (RAFT) approach. Since the development and use of the first non-viral vector for gene delivery applications, a wide range of polymers were synthesized and studied for their gene delivery efficacies. With the advent of living radical polymerization (LRP), well-defined polymers with varying molecular weights, compositions and architectures were synthesized to evaluate their potency as gene delivery vectors. Atom transfer radical polymerization (ATRP) and RAFT are two widely used LRP approaches for gene delivery applications. This review focuses primarily on the synthesis and use of cationic polymers via RAFT for DNA and siRNA delivery in vitro and in vivo. RAFT polymerization has allowed the facile synthesis of tailor-made cationic polymers with pendent biocompatible moieties which are promising non-viral gene delivery vectors. Advanced structure–activity relationship studies between the polymers and gene expression have been possible due to the remarkable control in the design of these polymers via the RAFT process. As a result, biocompatible and non-toxic polymers are produced under aqueous conditions and are identified as potent gene delivery vectors in vitro and in vivo. Polymeric functionalized nanomaterials were produced and studied for gene delivery applications. The consistency of results obtained from different research groups and identification of improved gene expression efficacies of RAFT based gene delivery vectors indicate the scope of this polymerization approach for future studies.
Research Interests: Engineering, DNA, CS, AFM, ATRP, and 11 morePll, CHEMICAL SCIENCES, Gene Delivery, PEG, Snp, siRNA, Structure activity Relationship, DLS, GFP, PSMA, and Raft
Inhibition of AB(5)-type bacterial toxins can be achieved by heterobifunctional ligands (BAITs) that mediate assembly of supramolecular complexes involving the toxin's pentameric cell membrane-binding subunit and an endogenous... more
Inhibition of AB(5)-type bacterial toxins can be achieved by heterobifunctional ligands (BAITs) that mediate assembly of supramolecular complexes involving the toxin's pentameric cell membrane-binding subunit and an endogenous protein, serum amyloid P component, of the innate immune system. Effective in vivo protection from Shiga toxin Type 1 (Stx1) is achieved by polymer-bound, heterobifunctional inhibitors-adaptors (PolyBAITs), which exhibit prolonged half-life in circulation and by mediating formation of face-to-face SAP-AB(5) complexes, block receptor recognition sites and redirect toxins to the spleen and liver for degradation. Direct correlation between solid-phase activity and protective dose of PolyBAITs both in the cytotoxicity assay and in vivo indicate that the mechanism of protection from intoxication is inhibition of toxin binding to the host cell membrane. The polymeric scaffold influences the activity not only by clustering active binding fragments but also by ste...
Research Interests: Transgenic Mice, Mice, Animals, Toxins, Shiga Toxin, and 4 moreAcrylic Resins, Cell Survival, Ligands, and Vero cells
In this study statistical glyco-dithiocarbamate (DTC) copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently used to prepare glyconanoparticles and conjugated... more
In this study statistical glyco-dithiocarbamate (DTC) copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently used to prepare glyconanoparticles and conjugated glyconanoparticles with the anti-cancer drug, gold(I) triphenylphosphine. These glyconanoparticles and the corresponding conjugates were then tested for their in vitro cytotoxicity in both normal and cancer cell lines using Neutral Red assay. The glyconanoparticles and their Au(I)PPh3 conjugates were all active against MCF7 and HepG2 cells, but galactose-functionalized glyconanoparticles {P(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP} were found to be the most cytotoxic to HepG2 cells (IC50 4.13 ± 0.73 g/mL). The p(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP was found to be 4-fold more potent anti-tumor agent in HepG2 cells and the overexpressed asialoglycoprotein (ASGPR) receptors revealed to play an important role in the enhanced uptake and toxicity. In addition, the glyconanopart...
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The facile encapsulation of biomolecules along with efficient formulation and storage makes nanogels ideal candidates for drug and gene delivery. So far, nanogels have not been used for the codelivery of plasmid DNA and proteins due to... more
The facile encapsulation of biomolecules along with efficient formulation and storage makes nanogels ideal candidates for drug and gene delivery. So far, nanogels have not been used for the codelivery of plasmid DNA and proteins due to several limitations, including low encapsulation efficacy of biomolecule of similar charges and the size of cargo materials. In this study, temperature and pH sensitive carbohydrate-based nanogels are synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization technique and are studied in detail for their capacity to encapsulate and codeliver plasmid DNA and proteins. The temperature sensitive property of nanogels allows the facile encapsulation of biomaterials, while its acid-degradable profile allows the burst release of biomolecules in endosomes. Hence these materials are expected to serve as efficient vectors to deliver biomolecules of choice either alone or as codelivery system. The nanogels produced are relatively monodisperse and are around 30-40 nm in diameter at 37 °C. DNA condensation efficacy of the nanogels is dependent on the hydrophobic property of the core of the nanogels. The DNA-nanogel complexes are formed by the interaction of carbohydrate residues of nanogels with the DNA, and complexes are further stabilized with linear cationic glycopolymers. The DNA-nanogels complexes are also studied for their protein loading capacity. The degradation of the nanogels and the controlled release of DNA and proteins are then studied in vitro. Furthermore, the addition of a nontoxic, cationic glycopolymer to the nanogel-DNA complexes is found to improve the cellular uptake and hence to improve gene expression.