The suitable size of multifunctional nanomedicines strongly influences their physicochemical properties and actions in biological systems, for example, prolonged blood circulation time, efficient tumor accumulation, and deep tumor penetration. However, it is still a great challenge to construct size‐transformable nanoparticles (NPs) for both efficient accumulation and penetration throughout tumor tissue. Herein, a size‐transformed multifunctional NP is developed through a simple bicomponent assembling strategy for enhanced tumor penetration and efficient photo‐chemo combined antitumor therapy, due to the acidic tumor microenvironment and near infrared‐laser irradiation induced size‐shrink. This multifunctional bicomponent NP (PP NP) driven by electrostatic interaction is composed of negatively charged peptide amphiphile (PA1) and positively charged peptide prodrug (PA2). PP NPs (≈170 nm) have been proven to improve blood circulation time and stability in biological environments. Interestingly, PP NPs can reassemble small NPs (<30 nm) by responding to acidic tumor microenvironment and near‐infrared laser irradiation, which facilitates deep tumor penetration and improves cellular internalization. By integrating fluorescence imaging, tumor targeting, deep tumor penetration, and combined photo‐chemotherapy, PP NPs exhibit excellent in vivo antitumor efficacy. This study might provide an insight for developing a bicomponent assembling system with efficient tumor penetration and multimode for antitumor therapy.

Bacterial infection can delay wound healing, causing wounds to deteriorate and even threaten the patient's life. Recently, although many composite hydrogels as wound dressing have been developed, it is still highly desired to construct photothermal hydrogels with antimicrobial and antioxidant properties to accelerate the infected wound healing. In this work, a hyaluronic acid (HA)‐based composite hydrogel consisting of a dopamine‐substituted antimicrobial peptide (DAP) and Iron (III) ions is developed, which exhibits photothermal‐assisted promotion and acceleration of healing process of bacteria‐infected wounds. DAP, serving as both antimicrobial agent and ROS‐scavenger, forms Schiff's base bonds with aldehyde hyaluronic acid (AHA) and iron‐catechol coordination bonds to reinforce the composite hydrogel. The presence of Fe3+ can also promote covalent polymerization of dopamine, which endows the hydrogel with photothermal capacity. The in vitro and in vivo experiments prove that the composite hydrogel can effectively accelerate the infected wound healing process, including antibacterial, accelerated collagen deposition, and re‐epithelization. This study suggests that the multifunctional composite hydrogel possesses remarkable potential for bacteria‐infected wound healing by combining inherent antimicrobial activity, antioxidant capability, and photothermal effect.

In order to artificially regulate cell behaviors, intracellular polymerization as an emerging chemical technique has attracted much attention. Yet, it is still a challenge to achieve effective intracellular polymerization to conquer tumors in the complex cellular environment. Herein, this work develops a tumor‐targeting and caspase‐3 responsive nanoparticle composed of a diacetylene‐containing lipidated peptide amphiphile and mitochondria‐targeting photosensitizer (C3), which undergoes nanoparticle‐to‐nanofiber transformation and efficient in situ polymerization triggered by photodynamic treatment and activation of caspase‐3. The locational nanofibers on the mitochondria membranes lead to mitochondrial reactive oxygen species (mtROS) burst and self‐amplified circulation, offering persistent high oxidative stress to induce cell apoptosis. This study provides a strategy for greatly enhanced antitumor therapeutic efficacy through mtROS burst and self‐amplified circulation induced by intracellular transformation and in situ polymerization.

Precise control of diacetylene-containing peptide amphiphile (DPA) based supramolecular architectures is important for their in cellulo polymerization behaviors and biomedical applications. Herein, we reported two DPAs (cationic PA-NH 2 and zwitterionic PA-OH) with a similar molecular structure, which exhibited completely opposite polymerization behaviors in aqueous solution and living cells. Specifically, PA-NH 2 was unpolymerizable in aqueous solution but underwent in cellulo polymerization to respond to the intracellular microenvironment. On the contrary, zwitterionic PA-OH was polymerized in solution, rather than inside living cells. Based on the results of cell viability and total internal reflection fluorescent microscopy measurement, PA-OH exhibited higher affinity with cell membranes and lower cytotoxicity than those of PA-NH 2 . Therefore, it is suggested that the in cellulo polymerization of PA-NH 2 should be responsive for greater cytotoxicity, rather than the membrane affinity. This study provides an in-depth understanding of the role of charge properties in the polymerization behavior of DPAs and seeks their potential biomedical applications.

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