ABSTRACT
Carrier-free nanomedicines offer advantages of extremely high drug loading capacity (>80%), minimal non-drug constituent burden, and facile preparation processes. Numerous studies have proved that multimodal cancer therapy can enhance chemotherapy efficiency and mitigate multi-drug resistance (MDR) through synergistic therapeutic effects. Upon penetration into the tumor matrix, nanoparticles (NPs) are anticipated to be uptaken by cancer cells, primarily through clathrin-meditated endocytosis pathways, leading to their accumulation in endosomes/lysosomes within cells. However, endo/lysosomes exhibit a highly degradative environment for organic NPs and drug molecules, often resulting in treatment failure. Hence, this study designed a lysosomal escape mechanism with carrier-free nanomedicine, combining the chemotherapeutic drug, curcumin (Cur), and the photothermal/photodynamic therapeutic drug, indocyanine green (ICG), for synergistic cancer treatment (ICG-Cur NPs) via a facile preparation process. To facilitate endo/lysosomal escape, ICG-Cur NPs were modified with metal-phenolic networks (MPNs) of different thickness. The results indicate that a thick MPN coating promotes rapid endo/lysosomal escape of ICG-Cur NPs within 4 h and enhances the photothermal conversion efficiency of ICG-Cur NPs by 55.8%, significantly improving anticancer efficacy in both chemo- and photo-therapies within 3D solid tumor models. This finding underscores the critical role of endo/lysosomal escape capacity in carrier-free drug NPs for therapeutic outcomes and offers a facile solution to achieve it.
Subject(s)
Antineoplastic Agents , Curcumin , Indocyanine Green , Lysosomes , Lysosomes/metabolism , Lysosomes/drug effects , Humans , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Animals , Curcumin/chemistry , Curcumin/pharmacology , Mice , Nanoparticles/chemistry , Nanomedicine , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Drug Screening Assays, Antitumor , Endosomes/metabolism , Photochemotherapy , Cell Survival/drug effects , Particle Size , Cell Proliferation/drug effects , Mice, Inbred BALB C , Cell Line, Tumor , Female , Neoplasms/drug therapyABSTRACT
Much work has been done to understand the factors that impact photonic band-edge liquid crystal (LC) laser threshold and slope efficiency, two parameters often stated to quantify performance. Conventionally, LC lasers are optically pumped using Q-switched lasers with a fixed pulse duration, and thus the effect of pump pulse duration on LC laser performance has received little attention. While some studies have been published at different pump pulse durations, these use different laser sources and experimental conditions, making the data incomparable. By exploiting a recent breakthrough in laser diode pumping, our experimental results prove and quantify the detrimental effect of an increase in pump pulse duration on LC laser performance. We also show that the dependency of threshold on pump pulse duration depends on how threshold is defined, owing to an ambiguity in the definition of pulse energy in systems where peak power and pulse duration can be independently controlled. For improved comparison within the literature on LC laser device performance, we thus propose an alternative convention, whereby threshold is stated in units of peak power density.