Abstract:Disulfiram
(DSF), a U.S. Food and Drug Administration (FDA)-approved
drug for the treatment of chronic alcoholism, is also used as an antitumor
drug in combination with Cu2+ ions. However, studies have
shown that the endogenous Cu2+ dose in tumor tissues is
still insufficient to form relatively high levels of a bis(N,N-diethyldithiocarbamate) copper(II)
complex (denoted as Cu(DTC)2) to selectively eradicate
cancer cells. Here, DSF-loaded hollow copper sulfide nanoparticles
(DSF@PEG-HCuSNPs) were designed to… Show more
“…The CuS NPs were fabricated by using a facile two‐step synthesis method reported previously. [ 21 ] As observed from the transmission electron microscope (TEM) and scanning electron microscope (SEM) images, the as‐prepared CuS NPs exhibit a uniform spherical morphology with hollow cavities and the average diameter is around 150 nm ( Figure 1 a,b ). The energy dispersive X‐ray spectroscopy (EDS) element mapping also clearly demonstrates the uniform distribution of Cu and S elements in the hollow CuS structure (Figure 1c ).…”
Variant modalities are quested and merged into the tumor nanotherapy by leveraging the excitation from external or intratumoral incentives. However, the ubiquitous hypoxia and the insufficient content of hydrogen peroxide (H2O2) in tumor microenvironments inevitably hinder the effective production of reactive oxygen species (ROS). To radically extricate from the shackles, peroxymonosulfate (PMS: HSO5−)‐loaded hollow mesoporous copper sulfide (CuS) nanoparticles (NPs) are prepared as the distinct ROS donors for sulfate radical (•SO4−)‐mediated and stimuli‐responsive tumor nanotherapy in an oxygen‐independent manner. In this therapeutic modality, the second near‐infrared laser irradiation, together with the released copper ions as well as the heat produced by CuS after illumination, work together to activate PMS thus triply ensuring the copious production of •SO4−. Different from conventional ROS, the emergence of •SO4−, possessing a longer half‐life and more rapid reaction, is independent of the oxygen (O2) and H2O2 content within the tumor. In addition, this engineered nanosystem also exerts the function of photoacoustic imaging and skin restoration on the corresponding animal models. This study reveals the enormous potential of sulfate radical in oncotherapy and broadens pave for exploring the application of multifunctional and stimuli‐responsive nanosystems in biomedicine.
“…The CuS NPs were fabricated by using a facile two‐step synthesis method reported previously. [ 21 ] As observed from the transmission electron microscope (TEM) and scanning electron microscope (SEM) images, the as‐prepared CuS NPs exhibit a uniform spherical morphology with hollow cavities and the average diameter is around 150 nm ( Figure 1 a,b ). The energy dispersive X‐ray spectroscopy (EDS) element mapping also clearly demonstrates the uniform distribution of Cu and S elements in the hollow CuS structure (Figure 1c ).…”
Variant modalities are quested and merged into the tumor nanotherapy by leveraging the excitation from external or intratumoral incentives. However, the ubiquitous hypoxia and the insufficient content of hydrogen peroxide (H2O2) in tumor microenvironments inevitably hinder the effective production of reactive oxygen species (ROS). To radically extricate from the shackles, peroxymonosulfate (PMS: HSO5−)‐loaded hollow mesoporous copper sulfide (CuS) nanoparticles (NPs) are prepared as the distinct ROS donors for sulfate radical (•SO4−)‐mediated and stimuli‐responsive tumor nanotherapy in an oxygen‐independent manner. In this therapeutic modality, the second near‐infrared laser irradiation, together with the released copper ions as well as the heat produced by CuS after illumination, work together to activate PMS thus triply ensuring the copious production of •SO4−. Different from conventional ROS, the emergence of •SO4−, possessing a longer half‐life and more rapid reaction, is independent of the oxygen (O2) and H2O2 content within the tumor. In addition, this engineered nanosystem also exerts the function of photoacoustic imaging and skin restoration on the corresponding animal models. This study reveals the enormous potential of sulfate radical in oncotherapy and broadens pave for exploring the application of multifunctional and stimuli‐responsive nanosystems in biomedicine.
“…More importantly, the calculated photothermal conversion efficiency of HPDC NPs was 28.9% (Figs. 1 J and K), which was even better than that of many photothermal conversion nanoagents, including HCuSNPs (23.8%) [ 51 ], AIPH@Nb2C@mSiO2 NPs (27.03%) [ 52 ], and living photosynthetic bacteria (PSB) (27.3%) [ 53 ]. These results indicated that HPDC NPs could be used as a potential photothermal agent for future photothermal therapy attributing to its prominent photothermal conversion performance.…”
Background
Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy.
Results
Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy.
Conclusions
The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation.
Graphical Abstract
“…In a follow-up study, were Liu et al designed and prepared DSF-loaded hollow copper sulfide nanoparticles (DSF@PEG-HCuSNPs) to achieve photonic hyperthermia-amplified cancer chemotherapy of DSF, further validating the remarkable synergetic effects between the chemical reactions-triggered DSF chemotherapy and PTT. [ 38 ]. Fig.…”
Section: Nanomedicine-instructed Chemotherapy Synergistic Cancer Therapymentioning
Chemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible.
Graphical Abstract
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