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Updated: Nov 3, 2025
Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Cationic Polyporphyrins as siRNA Delivery Vectors for Photodynamic and Gene Synergistic Anticancer Therapy
Nan Zheng1, Xiaoqin Luo2, Zhiyi Zhang1
1State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, P. R. China.
Abstract:
Successful gene therapy is highly dependent on the efficiency of gene delivery, which is mostly achieved by the carrier. Current gene carriers are generally nontherapeutic and take over most of the proportion in the delivery systems. Therefore, a library of polymerized and cationic photosensitive drugs (polyphotosensitizers, pPSs) with HIF-1α siRNA delivery capability is constructed to realize using "drug" to deliver "gene". The pPS component acts as both a therapeutic carrier for intracellular HIF-1α siRNA delivery and a photosensitive drug with photodynamic therapy (PDT). A reactive oxygen species (ROS)-cleavable linker is used to polymerize PS, allowing the successful segregation of PS monomers in space, avoiding the undesired aggregation-caused quenching (ACQ) effect and enhancing the in vitro and in vivo PDT effect. The complexes formed by pPSs and HIF-1α siRNA exhibited desired siRNA condensation and serum stability at the optimal conditions (pPSs with guanidines/siRNA weight ratio of 15), efficient intracellular internalization, and gene-silencing efficiency (60%) compared with commercial available transfection reagents (40%), as well as synergistic in vitro and in vivo phototoxicity for the combination PDT-gene therapy toward cancer treatment. This study provides a promising paradigm for the design of both the gene delivery carrier and the photosensitizer, as well as for broad utilities in the combination therapy toward cancer treatment.
Insights
This study introduces novel polyphotosensitizers (pPSs) that act as both drug and gene carrier for cancer therapy. These pPSs enable efficient delivery of HIF-1α siRNA and enhance photodynamic therapy, offering a synergistic treatment approach.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Gene therapy relies heavily on efficient gene delivery systems.
- Current gene carriers are often non-therapeutic and dominate delivery system composition.
- Developing multifunctional carriers that combine therapeutic and delivery functions is crucial.
Purpose of the Study:
- To construct a library of polymerized and cationic photosensitive drugs (pPSs) capable of delivering HIF-1α siRNA.
- To create a dual-function system where the carrier acts as both a photosensitizer for photodynamic therapy (PDT) and a gene delivery vehicle.
- To investigate the efficacy of this combined approach for cancer treatment.
Main Methods:
- Synthesized pPSs using a reactive oxygen species (ROS)-cleavable linker to polymerize photosensitizers (PS).
- Formed complexes of pPSs and HIF-1α siRNA, optimizing conditions for siRNA condensation and serum stability.
- Evaluated intracellular uptake, gene-silencing efficiency, and in vitro/in vivo phototoxicity.
Main Results:
- pPS-siRNA complexes showed efficient siRNA condensation and serum stability at a pPSs/siRNA weight ratio of 15.
- Achieved 60% gene-silencing efficiency, surpassing commercial transfection reagents (40%).
- Demonstrated synergistic in vitro and in vivo phototoxicity, indicating enhanced therapeutic effects.
Conclusions:
- Developed a novel pPS system for combined photodynamic therapy and gene therapy.
- The pPSs effectively deliver HIF-1α siRNA and enhance PDT, offering a promising strategy for cancer treatment.
- This work presents a new paradigm for designing multifunctional drug delivery systems for combination cancer therapy.
