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Despite continual progress in the technologies and regimens for cancer therapy, the treatment outcome of fatal metastatic breast cancer is far from satisfactory. Encouragingly, nanotechnology has emerged as a valuable tool to optimize drug delivery process in cancer therapy via preventing the cargos from degradation, improving the tumor-targeting efficiency, enhancing therapeutic agents’ retention in specific sites, and controlling drug release. In the last decade, several mechanisms of suppressing tumor metastasis by functional nano drug delivery systems (NDDSs) have been revealed and a guidance for the rational design of anti-metastasis NDDSs is summarized, which consist of three aspects: optimization of physiochemical properties, tumor microenvironment remodeling, and biomimetic strategies. A series of medicinal functional biomaterials and anti-metastatic breast cancer NDDSs constructed by our team are introduced in this review. It is hoped that better anti-metastasis strategies can be inspired and applied in clinic.

Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment. [ABSTRACT FROM AUTHOR]

The red blood cell membrane (RBCm) provides tight protection, lowers the immunogenicity, and prolongs the circulation time of drugs in vivo when acting as the coating of drug delivery systems. However, the cellular uptake and release of drugs are hindered by RBCm. Docetaxel (DTX) is the first‐line medicine for treating triple‐negative breast cancer (TNBC), but it induces tumor metastasis. To solve these dilemmas, in this study, the photosensitizer 1,1‐dioctadecyl‐3,3,3,3‐tetramethylindotricarbocyanine iodide (DiR)‐modified RBCm (DM) is prepared, which is coated onto a hybrid micelle consisting of the prodrugs of DTX and the anti‐metastasis agent calcitriol (CTL), obtaining a nanoparticle, named HDC‐DM. In a 4T1 tumor‐bearing mouse model, after injecting HDC‐DM, the intratumoral DTX and CTL concentrations are increased by 1.7 and 2.5 times compared with the free drug groups. After irradiating tumors with near‐infrared laser, DiR elicits the photothermal effect, triggering the rupture of RBCm and drug release, promoting drug penetration in tumors, and inducing immunogenic cell death. The tumor growth inhibition rate is 77%, and the formation of lung metastases is reduced by 82%, with good biocompatibility. It is suggested that the combination of phototherapy, chemotherapy, and anti‐metastatic therapy using HDC‐DM is expected to be a powerful strategy for treating TNBC. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy approaches such as programmed cell death‐1/programmed cell death‐ligand 1 (PD‐1/PD‐L1) checkpoint blockade and indoleamine 2,3‐dioxygenase (IDO) inhibition are proven to promote immune response against tumors. Unfortunately, their positive response rates are unsatisfactory due to complicated immunosuppressive mechanisms in the tumor microenvironment, which can probably be rescued by integrating multiple immunoregulators and chemotherapeutic agents together. To improve the combination therapy of metastatic breast cancer, a ternary heparanase (Hpa)‐sensitive micelle‐loaded monocyte delivery system, termed as HDNH@MC, is designed, exploiting the capacity of Ly6Chi monocytes to be recruited to tumor sites and the overexpression of Hpa in tumors. The prodrugs of the chemotherapeutic agent docetaxel and IDO inhibitor NLG919 are synthesized by conjugating them on the substrate of Hpa, heparan sulfate. Then the PD‐1/PD‐L1 inhibitor HY19991‐encapsulating prodrug micelle@Ly6Chi monocyte system is prepared. HNDH@MC elevates drug concentrations and relieves immunosuppression in tumors of 4T1 breast carcinomas mice model, thus enhancing the infiltration and activity of CD8+ T cells and presenting significant anti‐cancer effect. The lung metastasis is suppressed and the survival of mice is prolonged. HNDH@MC will be a promising option for treating metastatic breast cancer by synergy of tumor‐targeting chemotherapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Many immune cells are capable of homing to sites of disease and eradicating infections and abnormal cells. However, their efficacy is usually down-regulated in tumor microenvironments and it is difficult to boost. It is presumed that the anticancer activity of immune cells can be improved by integrating an additional therapeutic modality such as chemotherapy into the cells. Here, Ly6Chi monocytes armed with the paclitaxel (PTX)-loading pH-sensitive micelle (PM), termed as PM@MC, are prepared. The PM internalization does not significantly affect the properties of the host Ly6Chi monocytes. In the 4T1 metastatic breast cancer mice model, PM@MCs home to both primary tumor and the lung metastasis foci. PM@MC exhibit 15-fold higher intratumor PTX accumulation than the commercial PTX injection, and achieve a tumor inhibiting rate of 96.8% and a lung metastasis suppression rate of 99.2%. No significant change is recorded in histology of major organs and in hematological and biochemical parameters after PM@MC treatment. The pH-sensitive micelle/Ly6Chi monocyte drug delivery device thus has the application potential in the targeting therapy of breast cancer with metastasis. [ABSTRACT FROM AUTHOR]

Highlights from the article: Ly6Chi Monocytes Delivering pH-Sensitive Micelle Loading Paclitaxel Improve Targeting Therapy of Metastatic Breast Cancer GLO:OKZ/15aug19:adfm201904596-fig-0005.jpg PHOTO (COLOR): Biodistribution and pharmacokinetics of different formulations. a) Fluorescence images of tumors and tissues of mice at 1, 8, and 24 h after intravenously administrated with free DiR and PM and PM@MC loading DiR. b) The amounts of PTX in tumors and tissues at 1, 4, 8, and 24 h after intravenously administrated with Taxol, PM, and PM@MC. c) The plasma concentration-time curve of PTX after intravenously administration of Taxol, PM, and PM@MC. S1 Pharmacokinetic parameters of PTX in rats after intravenously injected with Taxol, PM and PM@MC at the dose of 2.8 mg PTX/kg.

Interleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non-specific stimulation of cancer cells. Herein, a nanovesicle termed DoxFILN, comprising a membrane presenting IL15/IL15 receptor α complexes (IL15c) and a core of doxorubicin-loaded ferritin (Dox-Fn) are reported. The DoxFILN significantly enhances the densities and activities of intratumoral CTLs and NK cells. Mechanistically, DoxFILN undergoes deshelling in the acidic tumor microenvironment, releasing Dox-Fn and membrane-bound IL15c. Dox-Fn selectively target transferrin receptors on cancerous cells, facilitating intracellular Dox release and inducing immunogenic cell death. Concurrently, membrane-bound IL15c recognizes and activates IL15 receptor β/γc heterodimers, leading to a remarkable increase in the proliferation and activation of CTLs (16-fold and 28-fold) and NK cells (37-fold and 50-fold). The IL15-displaying nanovesicle introduced here holds promise as a potential platform for immunochemotherapy in the treatment of cancer., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The gut microbiota exerts inhibitory effects on the occurrence and progression of colorectal cancer (CRC) through various mechanisms. Compared to traditional microbiota regulation methods, prebiotics and probiotics demonstrate significant advantages in terms of safety and patient adaptability. Their synergy not only improves the intestinal environment but also enhances the host's anti-tumor immune response. 5-Fluorouracil (5-FU) is a first-line chemotherapy drug that has a short half-life and low bioavailability. However, if administered in an untargeted manner, 5-FU also causes adverse reactions. Liposomes can improve the pharmacokinetic profile of drugs and provide targeted delivery to the tumor site, thereby reducing side effects. In this work, a 5-FU-loaded liposome is modified with the prebiotic xylan derivative Sxy and the probiotic Akkermansia muciniphila active phospholipid homolog 1,2-dipalmitoylphosphatidy-lethanolamine (DPPE) to construct FLSK. The latter effectively prolongs the intestinal transport and release of 5-FU, maintaining high drug concentrations at the tumor site. FLSK is found to inhibit tumor growth and significantly extends the survival period of mice. In addition, FLSK promotes anti-tumor immunity and regulation of the gut microbiota. Combining the merits of prebiotics and probiotics, FLSK provides a potential strategy for integrating chemotherapy with gut microbiota regulation therapy for the treatment of CRC., (© 2024 Wiley‐VCH GmbH.)