Anthocyan-rich foods have attracted lots of attention because of their potential biological and pharmacological applications. Anthocyanins richly exist in blueberry fruits and have been proved to possess various bioactive properties. Despite the potential application of anthocyanins in the food, pharmaceutical and cosmetic industries, their use is limited because of their relative instability. Recently, much attention has been given to a particular family of anthocyanin derivatives, the pyranoanthocyanins that have been indicated to have higher stability than the original anthocyanins. However, the anti-cancer activity of pyranoanthocyanins is largely unknown. The objective of this study was to conduct a comparative analysis on the stability and anti-cancer activities of anthocyanins, anthocyanidins and pyranoanthocyanidins. Pyranoanthocyanidins exhibited the highest stability in the pH range 3.0–9.0, while anthocyanidins had the strongest inhibition on HeLa cells among the three anthocyan pigments. All the anthocyan pigments could effectively induce cell cycle arrest at the G₂/M phase in conjunction with a marked increase in the expression of the p53 protein. Exposure of HeLa cells to three anthocyan pigments caused pronounced late apoptosis that might be involved in the activation of the p38 MAPK/p53 signaling pathway. These findings suggest that anthocyanidins and pyranoanthocyanidins might be more promising anti-cancer agents than anthocyanins and warrant further evaluation regarding the molecular mechanisms.

Chitosan nanoparticles (NPs) serve as useful multidrug delivery carriers in cancer chemotherapy. Chitosan has considerable potential in drug delivery systems (DDSs) for targeting tumor cells. Doxorubicin (DOX) has limited application due to its resistance and lack of specificity. Chitosan NPs have been used for DOX delivery because of their biocompatibility, biodegradability, drug encapsulation efficiency, and target specificity. In this review, various types of chitosan derivatives are discussed in DDSs to enhance the effectiveness of cancer treatments. Modified chitosan–DOX NP drug deliveries with other compounds also increase the penetration and efficiency of DOX against tumor cells. We also highlight the endogenous stimuli (pH, redox, enzyme) and exogenous stimuli (light, magnetic, ultrasound), and their positive effect on DOX drug delivery via chitosan NPs. Our study sheds light on the importance of chitosan NPs for DOX drug delivery in cancer treatment and may inspire the development of more effective approaches for cancer chemotherapy.

The use of combination therapies that employ a variety of cell death mechanisms has emerged as a promising avenue of research in the treatment of cancer. However, the optimization of therapeutic synergies when integrating different modes remains a significant challenge. To this end, we developed a multifunctional intelligent drug-carrying nanoparticle (DFMTCH NPs) based on the metal-organic framework MIL-100, loaded with doxorubicin (DOX) and disulfiram (DSF), coated with a Cu-tannic acid (Cu-TA) network and hyaluronic acid (HA), for the purpose of combined chemotherapy/chemodynamic/photothermal anti-cancer therapy. On the one hand, the DFMTCH NPs exhibited a range of therapeutic capabilities, including chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT), which collectively enhanced the anti-tumor efficacy of chemotherapeutic agents. In addition, DFMTCH NPs proved sensitive photoacoustic imaging (PAI) in image-guided therapy. On the other hand, DFMTCH NPs could produce reactive oxygen species (ROS) and consume glutathione (GSH) by amplifying cellular oxidative stress, while causing intracellular mitochondrial dysfunction, inducing effective cuproptosis/ferroptosis/apoptosis to inhibit tumor growth. Collectively, this work provided an innovative strategy for designing multifunctional nanoparticles for effective combination therapies to combat colorectal cancer (CRC).