Diabetic wounds are difficult to heal due to recurrent bacterial infection, decreased proliferation, and migration of epidermal and endothelial cells. This is related to impaired leukocyte function and low blood concentrations of H2S in diabetic patients. Herein, an antibacterial polymersome-based wound dressing spray was demonstrated for complete diabetic wound healing. The designed polymersome was self-assembled from poly­(ε-caprolactone)24-block-poly­[lysine15-stat-(S-aroylthiooxime)23] [PCL24-b-P­(Lys23-stat-SATO15)], where PCL is the hydrophobic membrane-forming block and P­(Lys-stat-SATO) acts as a hydrophilic stabilizer block. The polymersomes can penetrate and kill Gram-positive and Gram-negative bacteria because of the electrostatic interaction induced by the antibacterial P­(Lys23-stat-SATO15) block. Furthermore, the SATO segments are capable of long-term H2S generation by reacting with cysteine (up to 12 h). This promotes proliferation, migration of epidermal and endothelial cells, and angiogenesis. Overall, this polymersome-based wound dressing spray acts as a bacterial inhibitor and H2S generator and offers a fresh insight into the effective treatment of diabetic wounds.

Biosynthesis has been a diverse toolbox to develop bioactive molecules and materials, especially for fabricating modified peptides and their assemblies induced by enzymes. Although desired chemical structures and nanoarchitectures have been achieved, the subsequent interferences of peptide assemblies with organelles and the cellular pathways still remain unsolved important challenges. Herein, we developed a new tripeptide, phenylalanine–phenylalanine–tyrosine (Phe–Phe–Tyr, or FFY), which can be intracellularly oxidized and in situ self-assemble into nanoparticles with excellent interference capability with microtubules and ultimately reverse the drug resistance of melanoma. With the catalysis of tyrosinase, FFY was first oxidized to a melanin-like FFY dimer (mFFY) with a diquinone structure for further self-assembling into mFFY assemblies, which could inhibit the self-polymerization of tubulin to induce severe G2/M arrest (13.9% higher than control). Afterward, mitochondrial dysfunction was also induced for overproduction of cleaved caspase 3 (3.1 times higher than control) and cleaved PARP (6.3 times higher), achieving a high level of resistant reversing without chemotherapeutic drugs. In vivo studies showed that the resistant melanoma tumor volumes were reduced by 87.4% compared to control groups after FFY treatment by peritumoral injections. Overall, this tyrosinase-induced tripeptide assembly has been demonstrated with effective intrinsic apoptosis against drug-resistant melanoma, providing a new insight into utilizing biomolecules to interfere with organelles to activate certain apoptosis pathways for treatment of drug-resistant cancer.

The morphology of nanoparticles is closely related to their various applications. However, precise control over geometric parameters such as the lateral surface curvature (K) of nanorods still remains an important challenge. To address this issue, we propose a π–π interlocking effect for fabricating biodegradable nanorods with tailored lateral surface curvature. This interlocking effect originates from π–π interactions, provides noncovalent conformational locks among poly-γ-benzyl-l-glutamate (PBLG) chains, and plays a key role in the formation of these nanorods during self-assembly. This interlocking effect can be facilely manipulated by end-group engineering; different α end groups are introduced into PBLG homopolypeptides to afford nanorods with controlled lateral surface curvature. The stronger the π–π interlocking effect, the straighter the lateral surface of nanorods. Furthermore, a co-solvent strategy can be applied to facilely control the aspect ratio (Γ) of the nanorods with a straight lateral surface. Compared with other nanorods that are either based on nonbiodegradable materials or dependent upon complicated cost-consuming processes, this work provides a versatile bottom-up strategy for preparing biodegradable nanorods with controlled lateral surface curvature and aspect ratio.

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