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.
Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse events associated with the use of telaprevir among patients with chronic hepatitis C virus infection, and cautious use of telaprevir is warranted.
Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse events associated with the use of telaprevir among patients with chronic hepatitis C virus infection, and cautious use of telaprevir is warranted.
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