The active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxycamptothecin (SN38), is 100– 1000 times more active than CPT-11 and has shown inhibitory effects on a range of cancer cells, including those from the rectal, small cell lung, breast, esophageal, uterine, and ovarian malignancies. Despite SN38’s potent anticancer properties, its hydrophobicity and pH instability have caused substantial side effects and anticancer activity loss, which make it difficult to use in clinical settings. To solve the above problems, the construction of SN38-based drug delivery systems is one of the most feasible methods to improve drug solubility, enhance drug stability, increase drug targeting ability, improve drug bioavailability, enhance therapeutic efficacy and reduce adverse drug reactions. Therefore, based on the targeting mechanism of drug delivery systems, this paper reviews SN38 drug delivery systems, including polymeric micelles, liposomal nanoparticles, polymeric nanoparticles, protein nanoparticles, conjugated drug delivery systems targeted by aptamers and ligands, antibody-drug couplings, magnetic targeting, photosensitive targeting, redox-sensitive and multi-stimulus-responsive drug delivery systems, and co-loaded drug delivery systems. The focus of this review is on nanocarrier-based SN38 drug delivery systems. We hope to provide a reference for the clinical translation and application of novel SN38 medications.

Elemene (ELE) is a group of broad-spectrum anticancer active ingredients with low toxicity extracted from traditional Chinese medicines (TCMs), such as Curcumae Rhizoma and Curcuma Radix, which can exert antitumour activities by regulating various signal pathways and targets. However, the strong hydrophobicity, short half-life, low bioavailability and weak in vivo targeting ability of ELE restrict its use. Targeted drug delivery systems based on nanomaterials are among the most viable methods to overcome these shortcomings. In this review, we first summarize recent studies on the clinical uses of ELE as an adjunct antitumour drug. ELE-based combination strategies have great promise for enhancing efficacy, reducing adverse reactions, and improving patients' quality of life and immune function. Second, we summarize recent studies on the antitumour mechanisms of ELE and ELE-based combination strategies. The potential mechanisms include inducing pyroptosis and ferroptosis, promoting senescence, regulating METTL3-mediated m⁶A modification, suppressing the Warburg effect, and inducing apoptosis and cell cycle arrest. Most importantly, we comprehensively summarize studies on the combination of targeted drug delivery systems with ELE, including passively and actively targeted drug delivery systems, stimuli-responsive drug delivery systems, and codelivery systems for ELE combined with other therapies, which have great promise in improving drug bioavailability, increasing drug targeting ability, controlling drug release, enhancing drug efficacy, reducing drug adverse effects and reversing MDR. Our summary will provide a reference for the combination of TCMs such as ELE with advanced targeted drug delivery systems in the future.

Background: Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between Phl molecules results in poor water solubility and low bioavailability, and thus the scope of the clinical application of Phl is limited. Therefore, it is particularly important to improve the water solubility of Phl for its use to further combat or alleviate skin aging and oxidative damage and develop antioxidant products for the skin. The purpose of this study was to develop and evaluate a phloretin transfersome gel (PTG) preparation for transdermal drug delivery to improve the bioavailability of the drug and delay aging. Methods: Phloretin transfersomes (Phl-TFs) were prepared and optimized by the thin-film dispersion–ultrasonication method. Phl-TFs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The Log P method was used to determine the solubility of the Phl-TFs. The skin penetration ability of the prepared PTG was evaluated using the Franz diffusion cell method. In addition, the in vivo pharmacokinetics of PTG were studied in rats, and an antioxidant activity investigation was conducted using a D-gal rat model. Results: Phl-TFs were successfully prepared with a Soybean Phosphatidylcholine (SPC)/CHOL ratio of 2.7:1 w/v, a phloretin concentration of 1.3 mg/mL, a hydration time of 46 min, an ultrasound time of 5 min, and an ultrasound power of 180 W. The Log P was 2.26, which was significantly higher than that of phloretin (p < 0.05, paired t test). The results of the in vitro penetration test demonstrated that the cumulative skin penetration of the Phl-TFs after 24 h was 842.73 ± 20.86 μg/cm². The data from an in vivo pharmacokinetic study showed that the C_max and AUC of PTG were 1.39- and 1.97-fold higher than those of the phloretin solution gel (PSG), respectively (p < 0.05, paired t test). The experimental results in aging rats showed that PTG had a better antioxidant effect. Conclusions: Phl-TFs and PTG preparations with a good shape, safety, and stability were successfully prepared. In vivo pharmacokinetics and preliminary antioxidant experiments further verified the transdermal penetration and antioxidant activity of the phloretin transdermal drug delivery preparation, providing an experimental basis for its further development.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the loss or low expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR). Due to the lack of clear therapeutic targets, paclitaxel (PTX) is often used as a first-line standard chemotherapy drug for the treatment of high-risk and locally advanced TNBC. PTX is a diterpenoid alkaloid extracted and purified from Taxus plants, functioning as an anticancer agent by inducing and promoting tubulin polymerization, inhibiting spindle formation in cancer cells, and preventing mitosis. However, its clinical application is limited by low solubility and high toxicity. Nanodrug delivery system (NDDS) is one of the feasible methods to improve the water solubility of PTX and reduce side effects. In this review, we summarize the latest advancements in PTX-targeted NDDS, as well as its combination with other codelivery therapies for TNBC treatment. NDDS includes passive targeting, active targeting, stimuli-responsive, codelivery, and multimode strategies. These systems have good prospects in improving the bioavailability of PTX, enhancing tumor targeting, reducing toxicity, controlling drug release, and reverse tumor multidrug resistance (MDR). This review provides valuable insights into the clinical development and application of PTX-targeted NDDS in the treatment of TNBC.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic effects on the treatment of various cancers and cancer pain as adjuvant antitumor drugs in clinical practice. The involved mechanisms include inducing apoptosis, arresting the cell cycle, inhibiting cell proliferation, migration and invasion, inhibiting tumor angiogenesis, reversing the multidrug resistance of tumor cells, and regulating multiple signaling pathways and targets. Moreover, a multidrug combination strategy based on a nanodelivery system can realize the precise loading of the active ingredients of toad skin or toad venom and other antitumor drugs and carry drugs to overcome physiological and pathological barriers, complete efficient enrichment in tumor tissues, and achieve targeted delivery to tumor cells and the controlled release of drugs, thus enhancing antitumor efficacy and reducing toxicity and side effects. This article reviewed the clinical efficacy and safety of the combination of toad skin and toad venom with chemotherapeutic drugs, targeted drugs, analgesics and other drugs; evaluated the effects and mechanisms of the combination of toad skin and toad venom with chemotherapy, targeted therapy, radiotherapy or hyperthermia, traditional Chinese medicine, signaling pathway inhibitors and other therapies in cell and animal models; and summarized the codelivery strategies for the active ingredients of toad skin and toad venom with chemotherapeutic drugs, small-molecule targeted drugs, monoclonal antibodies, active ingredients of traditional Chinese medicine, and photodynamic and photothermal therapeutic drugs to provide a basis for the rational drug use of toad skin and toad venom in the clinic and the development of novel drug delivery systems.