Phenylboronic Acid-Dopamine Dynamic Covalent Bond Involved Dual-Responsive Polymeric Complex: Construction and Anticancer Investigation.

In cancer treatment, prolonging the retention time of therapeutic agents in tumor tissues is a key point in enhancing the therapeutic efficacy. However, drug delivery by intravenous injection is always subjected to a "CAPIR" cascade, including circulation, accumulation, penetration, internalization, and release. Intratumoral administration has gradually emerged as an ideal alternative approach for nanomedicine because of its independence of blood constituents and minimal systemic toxicities. In this contribution, based on the dynamically reversible interaction between boronic acid (BA) and dopamine (DA), a thermo- and pH-responsive polymeric complex is rationally obtained by facile mixing of phenylboronic acid (PBA)- and tetraphenylethene (TPE)-modified poly(N-isopropylacrylamide)-b-poly(phenyl isocyanide)s block copolymers, PNIPAM-b-P(PBAPI-co-TPEPI), and tetra(ethylene glycol) methyl ether acrylate (OEGA)- and DA-containing hydrophilic P(DA-co-OEGA) copolymers. The resultant complex exhibited temperature- and pH-dependent size change as well as sustained nile red (NR) release profiles in a mimic tumor environment. Moreover, thanks to the opposite optical behavior of TPE and NR molecules, the complex could be served as a fluorescence ratiometric cell imaging agent, avoiding the interference of background fluorescence and improving correlated resolution. After encapsulation of camptothecin (anticancer drug), the efficient killing on HeLa cells was achieved in vitro, and the structural integrity of the complex endowed its extended retention time in tumor tissues. Considering these advantages, the reversible covalent interaction between PBA and diols can be used as an efficient driving force to form dynamic drug-delivery vectors, which are promising to be an effective nanoplatform for injectable medical treatments.