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.

Positively charged helical chain-modified stimuli-responsive nanoassembly capable of targeted drug delivery and photoacoustic imaging-guided chemo-photothermal synergistic therapy.

In cancer treatment, surface modification by penetrating peptides and size control have been exploited as the two main strategies to tackle the problems of deep tumor penetration and cell internalization for nanocarriers. Polymeric nanocarriers with small size are beneficial for deep tumor penetration; however, they always undergo rapid clearance during body circulation and have low tumor accumulation efficiency. To solve this dilemma, a tumor-targeted size-switchable CPT/IR780@H30-PCL-PPI(L-)/PEI(-COOH/FA) nanoassembly with a "pomegranate" construction was designed in this study. Initially, it possessed a large size and negative charge to meet the long blood circulation time but rapidly disassembled into small-sized guanidinium and helical chain-modified unimolecular micelle-based nanocarriers, CPT/IR780@H30-PCL-PPI(L-/ + ), at tumor sites due to the tumor microenvironment-induced charge reversal. The CPT/IR780@H30-PCL-PPI(L-/+) assembly could efficiently expand the penetration depth and accelerate cell internalization due to the guanidinium group-modified helical chains, which exhibited a similar structure to that of the cell penetrating peptides. In addition, the nanoassembly exhibited strong photothermal conversion and acoustic generation efficiency. Moreover, the generated heat significantly improved the drug release, thus realizing functional cooperativity and adaptability. This proof of concept can be supposed to be a significant progress in the design and preparation of tumor microenvironment-responsive drug delivery systems and their use for photoacoustic imaging-assisted chemo-photothermal synergistic therapy.

[Effect of miR-542-3p on carcinogenesis induced by anti-benzo(a) pyrene-7,8-diol-9,10-epoxide].

OBJECTIVE: To explore the effect of miR-542-3p in malignant transformation of human bronchial epithelial cells (16HBE) induced by anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (anti-BPDE). METHODS: The relative expression level of mature miR-542-3p in transformed cells (16HBE-T) and untransformed control cells (16HBE-N) was measured by real-time quantitative polymerase chain reaction (qRT-PCR). miRNA mimic was transiently transfected into 16HBE-T to change the expression level of miR-542-3p, and then the influenced changes of cell proliferation, cell cycle, apoptosis, and soft agar colony formation rate and the migration of transfected cells were analyzed. RESULTS: Before transfection, the expression level of mature miR-542-3p in 16HBE-T was lower (39.08 ± 6.95)% than it in 16HBE-N (t = 15.18, P < 0.05). In comparison with the 16HBE-T group, the expression level of miR-542-3p in miR-542-3p mimic-transfected group was (5.23 ± 0.55) fold (t = 17.37, P < 0.05) after transfection. Cell proliferation of mimic-transfected group was decreased to (62.06 ± 5.61)% (t = -17.28, P < 0.05), percentage of cells in G(0)/G(1) phase up to (74.76 ± 4.86)% (t = 4.53, P < 0.05), rate of colony formation degrade to (5.87 ± 0.67)% (t = -6.66, P < 0.05), coverage areas ratio decreased to (0.31 ± 0.08) (t = -6.78, P < 0.05). There was no change with apoptosis. CONCLUSION: Our studies showed that miR-542-3p played the role as a tumor suppressor, which led to a significant decrease in the proliferation capacity and degree of malignancy. These findings suggest aberrantly down-regulated miR-542-3p may be one critical factor that contributes to malignant transformation of 16HBE induced by anti-BPDE.