期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 23, 页码 27513-27521出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c07662
关键词
photodynamic therapy; gene carrier; PDT-gene combination therapy; cationic polyphotosensitizers; synergistic anticancer treatment
资金
- National Science Foundation of China [51703018, 21978039]
- Special Funds of the Central Government Leading Local Government for the Technology Development [2021JH6/10500148, 2021JH6/10500146]
- Fundamental Research Funds for the Central Universities [DUT20YG120, DUT19LK60]
This study introduces a library of polymerized and cationic photosensitive drugs (pPSs) with HIF-1 alpha siRNA delivery capability for gene therapy. By using a ROS-cleavable linker, successful segregation of PS monomers was achieved, enhancing the PDT effect. The drug exhibited desired siRNA delivery and gene silencing both in vitro and in vivo.
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-1 alpha siRNA delivery capability is constructed to realize using drug to deliver gene. The pPS component acts as both a therapeutic carrier for intracellular HIF-1 alpha 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-1 alpha 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.
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