Multifunctional micelles loaded with the near-infrared (NIR) dye and labeled with the radionuclide rhenium-188 ((188)Re) have been developed to provide multimodalities for NIR fluorescence and nuclear imaging and for photothermal therapy (PTT) of cancer. The NIR dye, IR-780 iodide, allowed the micelles to have dual functions in cancer NIR imaging and PTT. The (188)Re-labeled IR-780 micelles enabled imaging by NIR fluorescence and by microSPECT to guide the delivery of drugs and to monitor in real-time the tumor accumulation, intratumoral distribution, and kinetics of drug release, which serve as a basis of specific photothermal injury to the targeted tissue. We also investigated the biodistribution, generation of heat, and photothermal cancer ablation of IR-780 micelles of both in vitro and in vivo xenografts. Histopathology observed irreversible tissue damage, such as necrotic features, decreased cell proliferation, increased apoptosis of cells, and increased expression of heat shock proteins in the PTT-treated tumors. The (188)Re-labeled IR-780 micelles offer multifunctional modalities for NIR fluorescence and nuclear imaging and for PTT of cancer.
The inner region
of solid tumors is found to be high-pressure,
hypoxic, and immunosuppressive, providing a breeding ground for tumor
aggressiveness and metastasis. While intratumoral accumulation of
nanomedicines combined with immunomodulation would significantly enhance
therapeutic efficacy, such potential is challenged by the compressed
environment and distinct heterogeneity of the tumor bulk. By using
an apoptotic body (AB) as the carrier, we develop an effective and
universal intratumoral nanomedicine delivery system for the long-lasting
remission of tumors. Our results show that the AB-encapsulated nanomedicine
(using CpG immunoadjuvant-modified gold–silver nanorods as
a model), after intravenous injection, can be specifically phagocytosed
by inflammatory Ly-6C+ monocytes, which then actively infiltrate
the tumor center via their natural tumor-homing tendency. With the
integration of AB-facilitated intratumoral accumulation, the nanorod-based
photothermal effect, and CpG-promoted immunostimulation, this cell-mediated
delivery system can not only efficiently ablate primary tumors but
also elicit a potent immunity to prevent tumors from metastasizing
and recurring.
Cancer stem-like cells play a key role in tumor development, and these cells are relevant to the failure of conventional chemotherapy. To achieve favorable therapy for colorectal cancer, PEG-PCL-based nanoparticles, which possess good biological compatibility, were fabricated as nanocarriers for the topoisomerase inhibitor, SN-38. For cancer stem cell therapy, CD133 (prominin-1) is a theoretical cancer stem-like cell (CSLC) marker for colorectal cancer and is a proposed therapeutic target. Cells with CD133 overexpression have demonstrated enhanced tumor-initiating ability and tumor relapse probability. To resolve the problem of chemotherapy failure, SN-38-loaded nanoparticles were conjugated with anti-CD133 antibody to target CD133-positive (CD133(+)) cells. In this study, anti-CD133 antibody-conjugated SN-38-loaded nanoparticles (CD133Ab-NPs-SN-38) efficiently bound to HCT116 cells, which overexpress CD133 glycoprotein. The cytotoxic effect of CD133Ab-NPs-SN-38 was greater than that of nontargeted nanoparticles (NPs-SN-38) in HCT116 cells. Furthermore, CD133Ab-NPs-SN-38 could target CD133(+) cells and inhibit colony formation compared with NPs-SN-38. In vivo studies in an HCT116 xenograft model revealed that CD133Ab-NPs-SN-38 suppressed tumor growth and retarded recurrence. A reduction in CD133 expression in HCT116 cells treated with CD133Ab-NPs-SN-38 was also observed in immunohistochemistry results. Therefore, this CD133-targeting nanoparticle delivery system could eliminate CD133-positive cells and is a potential cancer stem cell targeted therapy.
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