M2 macrophage microvesicle-inspired nanovehicles improve accessibility to cancer cells and cancer stem cells in tumors

Cancer cells and cancer stem cells (CSCs) are the major players of cancer malignancy and metastasis, but they are extremely difficult to access. Inspired by the vital role of macrophages and microvesicle-mediated cell–cell communication in tumors, we herein designed M2 macrophage microvesicle-inspired nanovehicle of cabazitaxel (M-CFN) to promote accessibility to cancer cells and CSCs in tumors. In the 4T1 tumor model, M-CFN flexibly permeated the tumor mass, accessed cancer cells and CD90-positive cells, and significantly promoted their entry into CSC fractions in tumors. Moreover, M-CFN treatment profoundly eliminated aldehyde dehydrogenase (ALDH)-expressing CSCs in 4T1 and MCF-7 tumors, produced notable depression of tumor growth and caused 93.86% suppression of lung metastasis in 4T1 models. Therefore, the M2 macrophage microvesicle-inspired nanovehicle provides an encouraging strategy to penetrate the tumor tissues and access these insult cells in tumors for effective cancer therapy. Graphical Abstract

Hematologic complications of immune checkpoint inhibitors

Immune checkpoint inhibitors are a class of anti-neoplastic therapies that unleash immune cells to kill malignant cells. There are currently 7 medications FDA-approved for the treatment of 14 solid tumors and 2 hematological malignancies. These medications commonly cause immune-related adverse effects due to overactive T lymphocytes, autoantibody production, and/or cytokine dysregulation. Hematological toxicities are rare and of uncertain mechanism, and therefore management is often based on experiences with familiar conditions involving these perturbed immune responses, such as autoimmune hemolytic anemia, immune thrombocytopenia, and idiopathic aplastic anemia. Management is challenging because one must attend to the hematological toxicity while simultaneously attending to the malignancy, with the imperative that effective cancer therapy be maintained or minimally interrupted if possible. The purpose of this review is to assist clinicians by providing a clinical and pathophysiological framework in which to view these problems.

Ferroptosis assassinates tumor (FAST)

In 2020, nearly 20 million peoples got cancer and nearly 10 million peoples died of cancer, indicating the current therapies do not meet the cancer treatment and cancer remains a great threat to human health and life. New therapies are still in urgent demand. In a recent study, we developed a new effective cancer therapy, gene-interfered ferroptosis therapy (GIFT), by combining cancer cell-specific knockdown of two iron efflux genes (FPN and LCN2) with iron nanoparticles (FeNPs). GIFT shows wide antitumor activity, high cancer specificity, certain cancer eradication potential, and biosafety. To further improve the therapy, we here develop an updated GIFT named as Ferroptosis ASsassinates Tumor (FAST) by knocking down five additional ferroptosis-resistance genes (FSP1, FTH1, GPX4, SLC7A11, NRF2). As a result, we found that FAST showed more significant antitumor activity than GIFT. Especially, FAST eradicated three different types of tumors (leukemia, colon cancer and lung metastatic melanoma) from over 50 percent of cancer mice, making the mice to survive up to 250 days without tumor relapse. FAST also significantly inhibited and prevented growth of spontaneous breast cancer and improved survival in mice. Additionally, FAST showed high pan-antitumor efficacy, high cancer specificity, and in vivo safety.

High Solubilization and Controlled Release of Paclitaxel Using Thermosponge Nanoparticles for Effective Cancer Therapy

Cancer, which is a leading cause of death, contributes significantly to reducing life expectancy worldwide. Even though paclitaxel (PTX) is known as one of the main anticancer drugs, it has several limitations, including low solubility in aqueous solutions, a limited dosage range, an insufficient release amount, and patient resistance. To overcome these limitations, we suggest the development of PTX-loaded thermosponge nanoparticles (PTX@TNP), which result in improved anticancer effects, via a simple nanoprecipitation method, which allows the preparation of PTX@TNPs with hydrophobic interactions without any chemical conjugation. Further, to improve the drug content and yield of the prepared complex, the co-organic solvent ratio was optimized. Thus, it was observed that the drug release rate increased as the drug capacity of PTX@TNPs increased. Furthermore, increasing PTX loading led to considerable anticancer activity against multidrug resistance (MDR)-related colorectal cancer cells (HCT 15), implying a synergistic anticancer effect. These results suggest that the solubilization of high drug amounts and the controlled release of poorly water-soluble PTX using TNPs could significantly improve its anticancer therapy, particularly in the treatment of MDR-p-glycoprotein-overexpressing cancers.

Recent Advances in Efficacy of Using Doxorubicin Gold Nanoparticles for Chemo-, Radio-, Photothermal, and Photodynamic therapy

: Nanoparticles (NPs) have been widely used in drug delivery systems specifically for chemo-, radio-, photothermal, and photodynamic therapy. Due to the lack of selectivity toward tumor cells the main target in therapies is to deliver drugs to cancer cells to reduce side effects. Gold nanoparticles (AuNPs) have been described as “promising nanocarriers for therapeutics” due to many properties such as low inherent toxicity, high water solubility and biocompatibility. Many research groups have focused on taking advantage of two or more therapies simultaneously to have increased efficacy using a lower dosage of the therapeutic drug and reduced multi drug resistance (MDR). Alternatively, doxorubicin (Dox) modification has been used as a strategy for increased selectivity toward target cells. Over the years, many studies have been performed on NPs to eliminate side effects using polymers, peptides, proteins, DNA, metallic NPs, microgels, and hydrogels on drug carrierse. In this review, recent advances of using Dox-AuNPs for chemo-, radio-, photothermal, photodynamic and combination therapy are briefly discussed, and we highlight recent progression in the application of Dox-AuNPs for effective cancer therapy.

PLGA Nanoparticles Decorated with Anti-HER2 Affibody for Targeted Delivery and Photoinduced Cell Death

The effect of enhanced permeability and retention is often not sufficient for highly effective cancer therapy with nanoparticles, and the development of active targeted drug delivery systems based on nanoparticles is probably the main direction of modern cancer medicine. To meet the challenge, we developed polymer PLGA nanoparticles loaded with fluorescent photosensitive xanthene dye, Rose Bengal, and decorated with HER2-recognizing artificial scaffold protein, affibody ZHER2:342. The obtained 170 nm PLGA nanoparticles possess both fluorescent and photosensitive properties. Namely, under irradiation with the green light of 540 nm nanoparticles, they produced reactive oxygen species leading to cancer cell death. The chemical conjugation of PLGA with anti-HER2 affibody resulted in the selective binding of nanoparticles only to HER2-overexpressing cancer cells. HER2 is a receptor tyrosine kinase that belongs to the EGFR/ERbB family and is overexpressed in 30% of breast cancers, thus serving as a clinically relevant oncomarker. However, the standard targeting molecules such as full-size antibodies possess serious drawbacks, such as high immunogenicity and the need for mammalian cell production. We believe that the developed affibody-decorated targeted photosensitive PLGA nanoparticles will provide new solutions for ongoing problems in cancer diagnostics and treatment, as well in cancer theranostics.