Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.

Paclitaxel (PTX) is the first natural plant-derived chemotherapeutic drug approved by the Food and Drug Administration. However, the clinical applications of PTX are limited by some drawbacks, such as poor water solubility, rapid blood clearance, nonspecific distribution, and adverse side effects. Nanocarriers have made important contributions to drug delivery and cancer therapy in recent years. However, low drug loading capacity, nanocarrier excipients-induced toxicity or immunogenicity, and complicated synthesis technologies pose a challenge for the clinical application of nanocarriers. To address these issues, the self-delivery nanomedicine (SDNs), in which pure drug molecules directly self-assemble into nanomedicine, have been developed for drug delivery and enhancing antitumor efficacy. In this review, we comprehensively summarize the recent advances in PTX-based SDNs for cancer therapy. First, the self-assembly strategies to develop pure PTX nanodrugs are discussed. Then, the emerging strategies of co-assembly PTX and other therapeutic agents for effective combination therapy are presented, composing of combination chemotherapy, chemo-photothermal therapy, chemo-photodynamic therapy, chemo-immunotherapy, and chemo-gene therapy. Finally, the limitations and future outlook of SDNs are discussed. The rational design of these unique nanoplatforms may make a new direction to develop highly efficient drug delivery systems for cancer therapy.

Photodynamic therapy (PDT) induces cancer cell death by utilizing photosensitizers to generate reactive oxygen species (ROS) upon light irradiation, which in turn trigger oxidative stress. However, the therapeutic efficacy of PDT is constrained by the short lifetimes and limited diffusion range of ROS, resulting in suboptimal outcomes and off-target effects. Specific organelle targeting, facilitated by rationally engineered photosensitizers and nanoplatforms with precise drug delivery capabilities that activate organelle-mediated cell death pathways, can maximize localized oxidative damage, enhance therapeutic efficacy, and minimize systemic toxicity. This review synthesizes advancements in organelle-targeted PDT, focusing on critical subcellular compartments (e.g., mitochondria, lysosomes, nuclei, cell membranes, ribosome, endoplasmic reticulum, golgi apparatus, autophagosome). It systematically summarizes the structural characteristics, design strategies, targeting mechanisms, and therapeutic effects of these organelle-targeted systems, with particular emphasis on organelle-mediated cell death signaling pathways. Ultimately, current challenges, prospective opportunities, and future research directions in organelle targeting are delineated, providing a strategic framework to advance organelle-targeted PDT toward precision therapy.