Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a potent anticancer drug with versatile biological activities, while the clinical translation of curcumin is severely limited due to its hydrophobicity, rapid elimination, and metabolism in the blood circulation. Herein, we aim to unravel the potential of curcumin as a synergistic agent with immunotherapy in the treatment of cancers. In an effort to minimize premature release and improve the systemic bioavailability, a superior blood stable and reduction sensitive curcumin micellar formulation, of which the release can be triggered by cancer cells, is rationally designed. We have synthesized a telodendrimer (mPEG-PLA-(LA)
4
) capable of forming reversible disulfide crosslinked micelles (DCMs). The curcumin loaded DCMs (Cur/DCMs) are spherical with a uniform size of 24.6 nm. The
in vitro
release profile demonstrates that curcumin releases significantly slower from DCMs than that from non-crosslinked micelles (NCMs), while the release can be accelerated with the increasing concentration of reducing agent glutathione (GSH). Intravenous administration of Cur/DCMs stably retains curcumin in the bloodstream and efficiently improves the systemic bioavailability. Furthermore, Cur/DCMs exhibit synergistic anticancer efficacy when combined with the anti-PD-1 antibody in an MC-38 colon cancer xenograft model. Our results potentiate the integration of blood stable curcumin nanoformulation and immunotherapy for cancer treatment.
Antibiotic-resistant bacterial infections have led to
an increased
demand for antibacterial agents that do not contribute to antimicrobial
resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic
structures have demonstrated remarkable effectiveness, including the
ability to suppress antibiotic resistance during bacterial treatment.
Herein, inspired by the facially amphiphilic structure of AMPs, the
facially amphiphilic skeletons of bile acids (BAs) are utilized as
building blocks to create a main-chain cationic bile acid polymer
(MCBAP) with macromolecular facial amphiphilicity via polycondensation
and a subsequent quaternization. The optimal MCBAP displays an effective
activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior
bactericidal stability in vitro, and potent anti-infectious performance
in vivo using the MRSA-infected wound model. MCBAP shows the low possibility
to develop drug-resistant bacteria after repeated exposure, which
may ascribe to the macromolecular facial amphiphilicity promoting
bacterial membrane disruption and the generation of reactive oxygen
species. The easy synthesis and low cost of MCBAP, the superior antimicrobial
performance, and the therapeutic potential in treating MRSA infection
altogether demonstrate that BAs are a promising group of building
blocks to mimic the facially amphiphilic structure of AMPs in treating
MRSA infection and alleviating antibiotic resistance.
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