Superparamagnetic Nanocrystals Clustered Using Poly(ethylene glycol)-Crosslinked Amphiphilic Copolymers for the Diagnosis of Liver Cancer.

Superparamagnetic iron oxide (SPIO) nanocrystals have been extensively studied as theranostic nanoparticles to increase transverse (T2) relaxivity and enhance contrast in magnetic resonance imaging (MRI). To improve the blood circulation time and enhance the diagnostic sensitivity of MRI contrast agents, we developed an amphiphilic copolymer, PCPZL, to effectively encapsulate SPIO nanocrystals. PCPZL was synthesized by crosslinking a polyethylene glycol (PEG)-based homobifunctional linker with a hydrophobic star-like poly(ε-benzyloxycarbonyl-L-lysine) segment. Consequently, it could self-assemble into shell-crosslinked micelles with enhanced colloidal stability in bloodstream circulation. Notably, PCPZL could effectively load SPIO nanocrystals with a high loading capacity of 66.0 ± 0.9%, forming SPIO nanoclusters with a diameter of approximately 100 nm, a high cluster density, and an impressive T2 relaxivity value 5.5 times higher than that of Resovist®. In vivo MRI measurements highlighted the rapid accumulation and contrast effects of SPIO-loaded PCPZL micelles in the livers of both healthy mice and nude mice with an orthotopic hepatocellular carcinoma tumor model. Moreover, the magnetic micelles remarkably enhanced the relative MRI signal difference between the tumor and normal liver tissues. Overall, our findings demonstrate that PCPZL significantly improves the stability and magnetic properties of SPIO nanocrystals, making SPIO-loaded PCPZL micelles promising MRI contrast agents for diagnosing liver diseases and cancers.

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.