Background: This study aimed to generate targeted folic acid-conjugated, doxorubicin-loaded, magnetic iron oxide bovine serum albumin nanospheres (FA-DOX-BSA MNPs) that lower the side effects and improve the therapeutic effect of antitumor drugs when combined with hyperthermia and targeting therapy. A new nanodrug using magnetic nanospheres for heating and addition of the folate receptor with cancer cell specificity was prepared. The characteristics of these nanospheres and their antitumor effects in nasopharyngeal carcinoma were explored. Methods: FA-DOX-BSA MNPs comprising encapsulated magnetic iron oxide nanoparticles were prepared using a desolvation cross-linking method. Activated folic acid (N-hydroxysuccinimide ester of folic acid) was conjugated to the surface of albumin nanospheres via amino groups. Results: Folic acid was successfully expressed on the surface of the nanospheres. Electron microscopy revealed that the FA-DOX-BSA MNPs were nearly spherical and uniform in size, with an average diameter of 180 nm. The nanomaterial could deliver doxorubicin at clinically relevant doses with an entrapment efficiency of 80%. An increasing temperature test revealed that incorporation of magnetic iron oxide into nanospheres could achieve a satisfactory heat treatment temperature at a significantly lower dose when placed in a high-frequency alternating magnetic field. FA-DOX-BSA MNPs showed greater inhibition of tumors than in the absence of folic acid in vitro and in vivo. Compared with chemotherapy alone, hyperthermia combined with chemotherapy was more effective against tumor cells. Conclusion: Folic acid-conjugated bovine serum albumin nanospheres composed of mixed doxorubicin and magnetic iron oxide cores can enable controlled and targeted delivery of anticancer drugs and may offer a promising alternative to targeted doxorubicin therapy for nasopharyngeal carcinoma.

Hepatocellular carcinoma (HCC) is frequently metastatic once diagnosed and less likely to respond to curative surgery, emphasizing the need for the development of more sensitive and effective diagnostic and therapeutic strategies. Epithelial cell adhesion molecule (EpCAM) is deemed as the biomarker of cancer stem cells (CSCs), which are mainly responsible for the recurrence, metastasis and prognosis of HCC. In this study, we discuss the use of mitoxantrone (MX), an antitumor drug and a photosensitizer, for designing upconversion nanoparticle-based micelles grafted with the anti-EpCAM antibody, for dual-modality magnetic resonance/upconversion luminescence (MR/UCL)-guided synergetic chemotherapy and photodynamic therapy (PDT). The obtained micelles exhibit good biocompatibility, high specificity to HCC cells and superior fluorescent/magnetic properties in vitro. In vivo results demonstrate that the targeted micelles exhibited much better MR/UCL imaging qualities compared to the nontargeted micelles after the intravenous injection. More importantly, PEGylated UCNP micelles loaded with MX and grafted with anti-EpCAM antibody, denoted as anti-EpCAM-UPGs-MX, showcased the most effective synergetic antitumor efficacy compared with other treatment groups both in vitro and vivo. The remarkable antitumor effect, coupled with superior simultaneous dual-modality MR/UCL imaging as well as good biocompatibility and negligible toxicity, makes the UPG micelles promising for future translational research in HCC diagnosis and therapy.

Background: Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood–brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and significantly increased survival time. Results: The Au-DOX@PO-ANG has a good ability to cross the blood–brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume. Conclusion: In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.

Background: Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy. Results: Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo. Conclusion: The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC. Graphic

Pancreatic cancer remains the leading cause of cancer-related deaths, the existence of cancer stem cells and lack of highly efficient early detection may account for the poor survival rate. Gadolinium ion-doped upconversion nanoparticles (UCNPs) provide opportunities for combining fluorescent with magnetic resonance imaging, and they can improve the diagnostic efficacy of early pancreatic cancer. In addition, as one transmembrane glycoprotein overexpressed on the pancreatic cancer stem cells, CD326 may act as a promising target. In this study, we developed a facile strategy for developing anti-human CD326-grafted UCNPs-based micelles and performed the corresponding characterizations. After conducting in vitro and vivo toxicology experiments, we also examined the active targeting capability of the micelles upon dual-mode imaging in vivo. We found that the micelles owned superior imaging properties and long-time stability based on multiple characterizations. By performing in vitro and vivo toxicology assay, the micelles had good biocompatibility. We observed more cellular uptake of the micelles with the help of anti-human CD326 grafted onto the micelles. Furthermore, we successfully concluded that CD326-conjugated micelles endowed promising active targeting ability by conducting dual-mode imaging in human pancreatic cancer xenograft mouse model. With good biocompatibility and excellent imaging properties of the micelles, our results uncover efficient active homing of those micelles after intravenous injection, and undoubtedly demonstrate the as-obtained micelles holds great potential for early pancreatic cancer diagnosis in the future and would pave the way for the following biomedical applications.

Purpose: To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods: CD90⁺ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90⁺ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results: CD90⁺ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90⁺ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90⁺ LCSCs to magnetic hyperthermia. Conclusion: The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo.