Pt(II)-PLGA Hybrid in a pH-Responsive Nanoparticle System Targeting Ovarian Cancer

Abstract

Platinum-based agents are the main treatment option in ovarian cancer (OC). Herein, we report a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) encapsulating platinum (II), which is targeted to a cell-spanning protein overexpressed in above 90% of late-stage OC, mucin 1 (MUC1). The NP is coated with phospholipid-DNA aptamers against MUC1 and a pH-sensitive PEG derivative containing an acid-labile hydrazone linkage. The pH-sensitive PEG serves as an off–on switch that provides shielding effects at the physiological pH and is shed at lower pH, thus exposing the MUC1 ligands. The pH-MUC1-Pt NPs are stable in the serum and display pH-dependent PEG cleavage and drug release. Moreover, the NPs effectively internalize in OC cells with higher accumulation at lower pH. The Pt (II) loading into the NP was accomplished via PLGA-Pt (II) coordination chemistry and was found to be 1.62 wt.%. In vitro screening using a panel of OC cell lines revealed that pH-MUC1-Pt NP has a greater effect in reducing cellular viability than carboplatin, a clinically relevant drug analogue. Biodistribution studies have demonstrated NP accumulation at tumor sites with effective Pt (II) delivery. Together, these results demonstrate a potential for pH-MUC1-Pt NP for the enhanced Pt (II) therapy of OC and other solid tumors currently treated with platinum agents.

Design and Application of Hybrid Polymer-Protein Systems in Cancer Therapy

“…As reported by Li et al [34], the generation of PCB-specific antibodies was minimal and insensitive to increasing protein immunogenicity. A pH-sensitive PEG derivative polymer, poly(lactic-co-glycolic acid) (PLGA), coated with phospholipid-DNA aptamers and an acidlabile hydrazone linkage was designed (Figure 2) [35]. The hybrid polymer encapsulating platinum (II) could target a cell-spanning protein overexpressed to more than 90% of latestage ovarian cancer, mucin 1 (MUC1), thus achieving enhanced cancer therapy.…”

Aptamer-Functionalized Nanoscale Metal–Organic Frameworks for Targeted Photothermal-Chemo Combined Tumor Therapy

“…Recently, significant advancements have been made in the field of nanotechnology, leading to the emergence of multimodal combinatorial therapy as an attractive choice. − Nanoscale metal–organic frameworks (MOFs) have attracted much attention in tumor therapy with large surface area, high porosity, and good biodegradability. − For example, MOF-199 could be utilized to design tumor PTT therapeutic platforms based on the local surface plasmon resonance (LSPR) effect in the NIR. ,− However, the efficiency of LSPR was limited, resulting in a poor curative effect of MOF-199. Moreover, as a type of semiconductor photosensitizer, CuS nanoparticles (NPs) could generate heat via the d–d* transition and plasmon resonance while absorbing light, thereby exhibiting considerable promise as antitumor agents. − The Wu group synthesized MOF-199, which was used for in situ sulfation of CuS NPs to enhance antibacterial activity.…”