Photoactivatable Prodrug-Backboned Polymeric Nanoparticles for Efficient Light-Controlled Gene Delivery and Synergistic Treatment of Platinum-Resistant Ovarian Cancer

Abstract

Combination of chemotherapy and gene therapy provides an effective strategy for cancer treatment. However, the lack of suitable codelivery systems with efficient endo/lysosomal escape and controllable drug release/gene unpacking is the major bottleneck for maximizing the combinational therapeutic efficacy. In this work, we developed a photoactivatable Pt­(IV) prodrug-backboned polymeric nanoparticle system (CNPPtCP/si(c‑fos)) for light-controlled si­(c-fos) delivery and synergistic photoactivated chemotherapy (PACT) and RNA interference (RNAi) on platinum-resistant ovarian cancer (PROC). Upon blue-light irradiation (430 nm), CNPPtCP/si(c‑fos) generates oxygen-independent N3 • with mild oxidation energy for efficient endo/lysosomal escape through N3 •-assisted photochemical internalization with less gene deactivation. Thereafter, along with Pt­(IV) prodrug activation, CNPPtCP/si(c‑fos) dissociates to release active Pt­(II) and unpack si­(c-fos) simultaneously. Both in vitro and in vivo results demonstrated that CNPPtCP/si(c‑fos) displayed excellent synergistic therapeutic efficacy on PROC with low toxicity. This PACT prodrug-backboned polymeric nanoplatform may provide a promising gene/drug codelivery tactic for treatment of various hard-to-tackle cancers.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy

“…The in vitro cell viability was detected by CCK-8 assay as previously reported [ 59 ]. In short, 4000 cells per well were incubated in a 96-well plate overnight.…”

Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting

“…The study provided a piece of evidence regarding enhanced cellular uptake and tumor-specific apoptosis through active targeting. In addition, the current concept of dual active and passive tumor targeting by dual cancer and gene therapy via light-responsive prodrugs or multiple stimuli-responsive prodrugs could be considered as a future prospect for the management of various types of malignancies [241].…”

Platinum(iv)-azido monocarboxylato complexes are photocytotoxic under irradiation with visible light

“…Hydroxido groups are common Pt( iv ) axial ligands because oxidation of Pt( ii ) to Pt( iv ) is readily accomplished through the use of H 2 O 2 and also due to the favourable solubility and stability properties imparted by inclusion of the hydroxido ligand. Derivatisation of one hydroxido ligand of a dihydroxido Pt( iv ) complex to a carboxylate can be achieved through a number of methods 19 including reaction with anhydrides, 20–23 acid chlorides, 24 and reaction with carboxylic acids in acetic acid solvent. 25 Terminal carboxylic acids which have been produced through reaction with anhydrides can be used to introduce targeting peptides.…”