Harnessing Phosphato-Platinum Bonding Induced Supramolecular Assembly for Systemic Cisplatin Delivery.

To improve the therapeutic index of cisplatin (CDDP), we present here a new paradigm of drug-induced self-assembly by harnessing phosphato-platinum complexation. Specifically, we show that a phosphato-platinum cross-linked micelle (PpY/Pt) can be generated by using a block copolymer methoxy-poly(ethylene glycol)-block-poly(l-phosphotyrosine) (mPEG-b-PpY). Coating of PpY/Pt with a R9-iRGD peptide by simple mixing affords a targeting micelle with near neutral-charged surface (iPpY/Pt). The micelles feature in well-controlled sizes below 50 nm and high stability under physiological conditions, and can withstand various environmental stresses. Importantly, the micelles demonstrate on-demand drug release profiles in response to pathological cues such as high ATP concentration and acidic pH. In vitro, the micelles are efficiently internalized and almost equally potent compared to CDDP. Moreover, iPpY/Pt induce greater cytotoxicity than PpY/Pt in a 3D tumor spheroid model likely due to its deeper tumor penetration. In vivo, the micelles exhibit prolonged circulation half-lives, enhanced tumor accumulation, excellent tumor growth inhibition in a xenograft HeLa model and an orthotropic mammary 4T1 model, and improved safety profiles evidenced by the reduced nephrotoxicity. Together, this work demonstrates for the first time that phosphato-platinum complexation can be exploited for effective delivery of CDDP, and suggests a paradigm shift of constructing nanosystems for other anticancer metallodrugs.

Rheological and structural characterization of HA/PVA-SbQ composites film-forming solutions and resulting films as affected by UV irradiation time.

Hyaluronan (HA)/poly (vinyl alcohol) bearing styrylpyridinium groups (PVA-SbQ) composites film-forming solutions were prepared by a negatively charged HA and an oppositely charged PVA-SbQ. The rheological properties and structural characterization of HA/PVA-SbQ composites in aqueous solution were investigated. Zeta potential measurements and TEM were utilized to explore the formation of HA/PVA-SbQ complex micelles in aqueous solution. UV spectra and DLS experiments confirmed that the micelles are photo-crosslinkable. HA/PVA-SbQ composites films were prepared by a casting method. The microstructure and properties of the film were analyzed by SEM, optical transmittance, DSC, XRD and tensile testing. The crosslinked HA/PVA-SbQ composites films exhibited higher UV light shielding and visible light transparency and better mechanical and water vapor barrier properties as well as thermal stability than the uncrosslinked HA/PVA-SbQ composites films, indicating the formation of three-dimensional network structure. This work provided a good way for increasing the mechanical, thermal, water vapor barrier, and optical properties of HA materials for the packaging material.