Hydrogels
serving as a drug carrier was realized by entrapping
small-sized drug molecules within their cross-linked interstitial
networks. After covering the targeted location, hydrogels interact
with the physiological fluids and swell, resulting in an increased
interspace between networks for the outside diffusion of drugs. However,
inevitable in vivo inflammatory responses or bacterial infection on
the implant materials and persistent cargo release are still challenging.
Herein, we report the fabrication of dual-responsive hydrogels based
on acid-sensitive poly(ethylenimine) (PEI) derivative (PEI(−COOH/–vinyl)),
thiol-responsive camptothecin prodrug monomer (CPTM), and hydrophilic
oligo(ethylene glycol) methyl ether acrylate (OEGMA) by a conventional
radical polymerization. Curcumin was then solubilized into the hydrogels
to endow them with antimicrobial and cancer resistance properties.
The in vitro experiments exhibited sustained hydrogel dissolution
and CPT release in a simulated physiological environment. The antimicrobial
and cytotoxicity tests of drug-loaded hydrogels using methicillin-resistant Staphylococcus aureus (MRSA) strains and HeLa cancer
cell lines, respectively, indicated that the hydrogels possessed efficient
antimicrobial effects and could successfully inhibit the growth of
cancer cells.
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.
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