Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy

Lin, Song; Jing, Houjin; Du, Xiaojiao; Yang, Xianzhu; Wang, Jun

doi:10.1039/d3bm02071a

Biomater. Sci.

2024

DOI: 10.1039/d3bm02071a

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Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy

Song Lin,

Houjin Jing,

Xiaojiao Du

et al.

Abstract: A siRNA delivery system was developed using clinically approved mPEG-b-PLGA, cationic lipid and ionizable lipid for siRNA delivery and cancer immunotherapy.

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2024

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Cited by 5 publications

References 32 publications

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Combinatorial Synthesis of Alkyl Chain‐Capped Poly(β‐Amino Ester)s for Effective siRNA Delivery

Chen,

Ren,

Jiang

et al. 2024

Macromolecular Bioscience

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Poly (β‐amino ester) (PBAE) is a class of biodegradable polymers containing ester bonds in their main chain, extensively investigated as cationic polymer carriers for siRNA. Most current PBAE carriers rely on termination with hydrophilic or charged amines. In this study, a polymer platform consisting of 168 PBAE polymers with hydrophobic alkyl chain terminals is constructed through sequential aza‐Michael addition. A large number of effective carriers are identified through in vitro screening of the PBAE platform for siLuc delivery to HeLa‐Luc cells. Specifically, PA8‐C6 and PA8‐C8 achieve remarkable gene knockdown efficacies of up to 80% with low cytotoxicity. Certain materials from the PA2 and PA5 series demonstrate potent siRNA delivery capabilities associated with elevated cytotoxicity. The pKa value of PBAE is predominantly determined by the hydrophilic amine side chains rather than the end‐capping groups. A pKa range of ≈6.2–6.5 may contribute to the excellent delivery capability for PA8 series carriers. The co‐formulation of PBAE carriers with helper lipids leads to the reduced size and surface charges of the polyplex NPs with siRNA, consequently decreasing the cytotoxicity and enhancing siRNA delivery efficacy. These findings hold significant implications for the development of novel degradable polymer carriers for siRNA delivery.

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Combinatorial Synthesis of Alkyl Chain‐Capped Poly(β‐Amino Ester)s for Effective siRNA Delivery

Chen,

Ren,

Jiang

et al. 2024

Macromolecular Bioscience

View full text Add to dashboard Cite

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Engineering an Ultrasound-Responsive Glycopolymersome for Hepatocyte-Specific Gene Delivery

Wei,

Chen,

Chen

2024

Biomacromolecules

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The ability to design liver-targeted gene delivery vectors is plagued with difficulties ranging from carrier-mediated cellular toxicity to challenges in encapsulating sensitive nucleic acids. Herein, we present an ultrasound-responsive glycopolymersome strategy for in situ loading of nucleic acids and achieving hepatocyte-specific gene delivery. This glycopolymersome is self-assembled from a block copolymer, N-acetylgalactosamine-grafted poly(glutamic acid)-block-poly(εcaprolactone) (PGAGalNAc-b-PCL). GalNAc is introduced to afford liver targeting through the selective binding to the asialoglycoprotein receptor overexpressed on hepatocytes. External ultrasound is utilized to assist in encapsulating nucleic acids within the hydrophilic lumen of glycopolymersomes by exploiting their ultrasound responsiveness nature. Biological studies confirmed the successful encapsulation of plasmid DNA (pDNA) and small interfering RNA (siRNA), rapid nuclear internalization, and efficient gene transfection. These findings collectively demonstrated that this ultrasound-responsive glycopolymersome could be exploited as a novel safe and efficient gene vector targeting hepatocytes.

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The potential of nanoparticle-based siRNA delivery in breast cancer treatment

Bakhtiar,

Kuan,

Chowdhury

2024

Nanomedicine

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Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy

Abstract: A siRNA delivery system was developed using clinically approved mPEG-b-PLGA, cationic lipid and ionizable lipid for siRNA delivery and cancer immunotherapy.

Cited by 5 publications

References 32 publications

Combinatorial Synthesis of Alkyl Chain‐Capped Poly(β‐Amino Ester)s for Effective siRNA Delivery

Combinatorial Synthesis of Alkyl Chain‐Capped Poly(β‐Amino Ester)s for Effective siRNA Delivery

Engineering an Ultrasound-Responsive Glycopolymersome for Hepatocyte-Specific Gene Delivery

The potential of nanoparticle-based siRNA delivery in breast cancer treatment

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