Construction of efficient doxorubicin (DOX) delivery systems addressing a cascade of physiological barriers remains a great challenge for better therapeutic efficacy of tumors. Herein, we design well-defined enzyme-responsive peptide-linked block copolymer, PEG-GPLGVRGDG-P(BLA-co-Asp) [PEG and P(BLA-co-Asp) are poly(ethylene glycol) and partially hydrolyzed poly(β-benzyl l-aspartate) (PBLA), respectively] (P3), with modular functionality for efficient delivery of DOX. The block copolymers were successfully obtained via click reaction to introduce peptide (alkynyl-GPLGVRGDG) into the end of PEG for initiating ring-opening polymerization of β-benzyl l-aspartate N-carboxyanhydride (BLA-NCA) by terminal amino groups followed by partial hydrolysis of PBLA segments. P3 micelle was demonstrated to encapsulate DOX efficiently through synergistic effect of benzyl group-based hydrophobic and carboxyl moiety-based electrostatic interactions. Effective matrix metalloproteinase-2 (MMP-2)-triggered cleavage of peptide for dePEGylation of P3 micelles was confirmed and residual RGD ligands were retained on the surfaces. Against HT1080 cells overexpressing MMP-2, DOX-loaded P3 micelles showed approximately 4-fold increase of the cellular internalization amount as compared with free DOX and half maximal inhibitory concentration (IC) value of DOX-loaded P3 micelles was determined to be 0.38 μg/mL compared with 0.66 μg/mL of free DOX due to MMP-triggered dePEGylation, RGD-mediated cellular uptake, and rapid drug release inside cells. Binding and penetration evaluation toward HT1080 multicellular tumor spheroids (MCTs) confirmed high affinity and deep penetration of P3 micelles in tumor tissues. This modular design of enzyme-responsive block copolymers represents an effective strategy to construct intelligent drug delivery vehicles for addressing a cascade of delivery barriers.

We report a sono‐Fenton strategy to mediate the supramolecular assembly of metal–phenolic networks (MPNs) as substrate‐independent coatings using phenol and phenyl derivatives as building blocks. The assembly process is initiated from the generation of hydroxyl radicals (.OH) using high‐frequency ultrasound (412 kHz), while the metal ions synergistically participate in the production of additional .OH for hydroxylation/phenolation of phenol and phenyl derivatives via the Fenton reaction and also coordinate with the phenolic compounds for film formation. The coating strategy is applicable to various phenol and phenyl derivatives and different metal ions including FeII, FeIII, CuII, and CoII. In addition, the sono‐Fenton strategy allows real‐time control over the assembly process by turning the high‐frequency ultrasound on or off. The properties of the building blocks are maintained in the formed films. This work provides an environmentally friendly and controllable method to expand the application of phenolic coatings for surface engineering.

Direct encapsulation of hydrophobic drugs into amphiphilic block copolymer micelles is frequently subjected to low drug loading efficiency (DLE) and loading content (DLC), as well as lower micellar stability and uncontrollable drug release. In this report, we prepare the copolymer prodrugs (PPEMA-co-PCPTM) via reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(piperidin-1-yl)ethyl methacrylate (PEMA) and reduction-responsive CPT monomer (CPTM), which were quantitatively encapsulated into poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles. The polymer prodrug-loaded nanoparticles showed high stability for a long time in aqueous solution or blood serum and even maintain similar size after a lyophilization-dissolution cycle. The tumoral pH (∼6.8)-responsive properties of PPEMA segments endow the micellar cores with triggered transition from neutral to positively charged and swellable properties. The PEG-b-PCL nanoparticles loading polymer prodrugs (PPEMA-b-PCPTM) eliminated burst drug release. Simultaneously, CPT drug release can be triggered by reductive agents and solution pH. At pH 6.8, efficient cellular internalization was achieved due to positively charged cores of the nanoparticles. As compared with nanoparticles loading PCPTM, higher cytotoxicity was observed by the nanoparticles loading PPEMA-b-PCPTM at pH 6.8. Further multicellular tumor spheroid (MCTs) penetration and growth suppression studies demonstrated that high-efficiency penetration capability and significant size shrinkage of MCTs were achieved after treatment by PPEMA-b-PCPTM-loaded nanoparticles at pH 6.8. Therefore, the responsive polymer prodrug encapsulation strategy represents an effective method to overcome the disadvantages of common hydrophobic drug encapsulation approaches by amphiphilic block copolymer micelles and simultaneously endows the nanoparticles with responsive drug release behaviors as well as enhanced cellular internalization and tumor penetration capability.

No abstract

Quantitative and accurate determination of iron ions play a vital role in maintaining environment and human health, but very few polymeric chemosensors were available for the detection of Fe3+ in aqueous solutions. Herein, a water-soluble rhodamine-poly (ethylene glycol) conjugate (DRF-PEG), as a dual responsive colorimetric and fluorescent polymeric sensor for Fe3+ detection with high biocompatibility, was first synthesized through Schiff base reaction between rhodamine 6G hydrazide and benzaldehyde-functionalized polyethylene glycol. As expected, the introduction of PEG segment in DRF-PEG significantly improved the water solubility of rhodamine derivatives and resulted in a good biosensing performance. The detection limit of DRF-PEG for Fe3+ in pure water is 1.00 μM as a fluorescent sensor and 3.16 μM as a colorimetric sensor at pH 6.5. The specific sensing mechanism of DRF-PEG toward Fe3+ is proposed based on the intramolecular charge transfer (ICT) mechanism, in which the O and N atoms in rhodamine moiety, together with the benzene groups from benzaldehyde-modified PEG segment, participate in coordination with Fe3+. Furthermore, DRF-PEG was applied for the ratiometric imaging of Fe3+ in HeLa cells and showed the potential for quantitative determination of Fe3+ in fetal bovine serum samples. This work provides insights for the design of water-soluble chemosensors, which can be implemented in iron-related biological sensing and clinical diagnosis.