Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers

Zhang, Yajie; Wang, Yafeng; Zhang, Chi; Wang, Jin; Pan, Dandan; Liu, Jianghuai; Feng, Fude

doi:10.1021/acsami.5b08119

Cited by 25 publications

(24 citation statements)

References 30 publications

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“…Among these, star shaped cationic polymers by integrating short chain cationic polymers onto biocompatible cores showed great practical potentials, due to their balanced control between cationic charge density determined cytotoxicity and gene encapsulation or transfection efficiency. For example, 1.8 kDa poly(ethylene imine) (PEI) was conjugated onto polyaspartamides cores to form cationic star polyaspartamides derivatives for successful transfection efficiency improvement on RAW264.7 macrophage cell line . We also utilized oligoethylenimine or poly(2‐dimethyl aminoethyl methacrylate) (PDMAEMA) to modify cyclic cyclodextrins (CDs) for formation of star shaped cationic polymers with satisfactory cytotoxicity and gene transfection performance, which opened a route for designing a safe and efficient pharmaceutical carrier for macrophages.…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages

Cheng

Fan

et al. 2018

Macromol. Rapid Commun.

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Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star-like amphiphilic biocompatible β-cyclodextrin-graft-(poly(ε-caprolactone)-block-poly(2-(dimethylamino) ethyl methacrylate) (β-CD-g-(PCL-b-PDMAEMA) ) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(ε-caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, β-CD-g-(PCL-b-PDMAEMA) copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by β-CD-g-(PCL-b-PDMAEMA) not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages

Cheng

Fan

et al. 2018

Macromol. Rapid Commun.

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“…Experimental results showed that the addition of dendrimers improved the transfection efficiency of plasmid DNA to macrophage by plasmid protection, which facilitated the switch of TAM to M1 macrophage. [ 114,115 ] More interestingly, M2 macrophage phenotype transformation can also be achieved by polymeric vectors. [ 116 ] For example, Tran et al.…”

Section: Targeted and Tumor Environment Responsive Gene Delivery Intomentioning

confidence: 99%

Polymeric Nonviral Gene Delivery Systems for Cancer Immunotherapy

Cai

et al. 2020

Advanced Therapeutics

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Unlike viral vectors with their undesired safety or immunogenicity concerns, biocompatible polymeric nonviral vectors as gene delivery systems are more promising in gene or cell therapy. Evidence has demonstrated that the rational design of polymeric nonviral gene vectors with optimal structure, charge density, biocompatibility, and stimulus responsiveness can deliver therapeutic genes or gene vaccines (in terms of deoxyribonucleic acid DNA or ribonucleic acid RNA) into tumor‐associated immunocytes (i.e., macrophages, T cells, or dendritic cells) in an effective and controllable manner for enhanced cancer immunotherapy. However, a timely and systematic summary of this subject is lacking. This review presents an overview of polymeric nonviral carriers with immune cell transfection ability and their potential applications in cancer immunotherapy; it also provides a tutorial for designing polymeric immune‐cell genetic modification vector, although there are still few vectors in the product pipeline. With the rapid growth of immunotherapy in cancer treatment and knowledge accumulation in vector structure design, polymeric nonviral gene delivery systems may provide new hope for tumor therapy.

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“…used mannosylated chitosan‐ graft ‐PEI polymer for a gene transfer in the same type of blood cells. [ 31 ] Linear PEI conjugated to mannan [ 32 ] and branched PEI conjugated to polyaspartamide derivatives modified with mannose and folic acid [ 33 ] were also explored as gene vectors. However, PEI homopolymer is not a good choice for in vivo transfection due to its poor bioavailability and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Mannosylated Cationic Copolymers for Gene Delivery to Macrophages

Lopukhov

Yang

Haney

et al. 2021

Macromolecular Bioscience

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Macrophages are desirable targets for gene therapy of cancer and other diseases. Cationic diblock copolymers of polyethylene glycol (PEG) and poly‐L‐lysine (PLL) or poly{N‐[N‐(2‐aminoethyl)‐2‐aminoethyl]aspartamide} (pAsp(DET)) are synthesized and used to form polyplexes with a plasmid DNA (pDNA) that are decorated with mannose moieties, serving as the targeting ligands for the C type lectin receptors displayed at the surface of macrophages. The PEG‐b‐PLL copolymers are known for its cytotoxicity, so PEG‐b‐PLL‐based polyplexes are cross‐linked using reducible reagent dithiobis(succinimidyl propionate) (DSP). The cross‐linked polyplexes display low toxicity to both mouse embryonic fibroblasts NIH/3T3 cell line and mouse bone marrow‐derived macrophages (BMMΦ). In macrophages mannose‐decorated polyplexes demonstrate an ≈8 times higher transfection efficiency. The cross‐linking of the polyplexes decrease the toxicity, but the transfection enhancement is moderate. The PEG‐b‐pAsp(DET) copolymers display low toxicity with respect to the IC‐21 murine macrophage cell line and are used for the production of non‐cross‐linked pDNA‐contained polyplexes. The obtained mannose modified polyplexes exhibit ca. 500‐times greater transfection activity in IC‐21 macrophages compared to the mannose‐free polyplexes. This result greatly exceeds the targeting gene transfer effects previously described using mannose receptor targeted non‐viral gene delivery systems. These results suggest that Man‐PEG‐b‐pAsp(DET)/pDNA polyplex is a potential vector for immune cells‐based gene therapy.

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Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers

Cited by 25 publications

References 30 publications

Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages

Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages

Polymeric Nonviral Gene Delivery Systems for Cancer Immunotherapy

Mannosylated Cationic Copolymers for Gene Delivery to Macrophages

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