Gold nanoparticles have been widely explored as cancer therapeutics and diagnostic agents in recent years. With their unique subcellular size and good biocompatibility, gold nanoparticles are a promising drug delivery vehicle. In this study, folic acid-coated gold nanoparticles conjugated with fluorophore FITC through amine terminated poly(ethylene glycol) were prepared and confocal microscopy together with bright-field differential interference contrast imaging data showed that folic acid-coated gold nanoparticles accumulated mainly in cytoplasm of primary human fibroblasts, without causing any observable cytotoxicity upon exposure for 48 hours. Through the further development of a drug delivery system that conjugates doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an SMCC linker, we demonstrated that multidrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and enhanced cytotoxicity of Au-SMCC-DOX nanoconjugates, as revealed both by confocal microscopy imaging and cytotoxicity assay. The prepared Au-SMCC-DOX nanoconjugates demonstrated enhanced drug accumulation and retention in multidrug resistant hepG2-R cancer cells when it was compared with free doxorubicin, with a cytoplasm accumulation profile. The results indicated that gold nanoparticles are a kind of promising drug delivery vehicle with good biocompatibility and suitable for further applications in drug delivery for improved chemotherapy, especially for overcoming multidrug resistance.
Metal phosphorous trichalcogenides (MPX3) are novel 2D nanomaterials that have recently been exploited as efficient photothermal–chemodynamic agents for cancer therapy. As a representative MPX3, FePSe3 has the potential to be developed as magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) agents due to the composition of Fe and the previously revealed PA signal. Here, a FePSe3‐based theranostic agent, FePSe3@APP@CCM, loaded with anti‐PD‐1 peptide (APP) as the inner component and CT26 cancer cell membrane (CCM) as the outer shell is reported, which acts as a multifunctional agent for MR and PA imaging and photothermal and immunotherapy against cancer. FePSe3@APP@CCM induces highly efficient tumor ablation and suppresses tumor growth by photothermal therapy under near‐infrared laser excitation, which further activates immune responses. Moreover, APP blocks the PD‐1/PD‐L1 pathway to activate cytotoxic T cells, causing strong anticancer immunity. The combined therapy significantly prolongs the lifespan of experimental mice. The multimodal imaging and synergistic therapeutic effects of PTT and its triggered immune responses and APP‐related immunotherapy are clearly demonstrated by in vitro and in vivo experiments. This work demonstrates the potential of MPX3‐based biomaterials as novel theranostic agents.
This novel synergy of the multispectral PAI technique and the activatable probe is a potential strategy for the distribution estimation of tumor protease activity in vivo.
Metastasis accounts for the vast majority of cancer deaths. To minimize metastasis-associated mortality, it is crucially important to evaluate the metastatic potential (M.P.), that is, defined as a tendency of a primary tumor to colonize a distant organ. Dysregulated pH in solid tumors, especially the acidification of extracellular pH (pH e ) promotes dormant metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and increasing migration of cancer cells. Therefore, imaging intratumoral acidosis creates a unique opportunity to evaluate the M.P. In this work, a novel pH activatable probe was developed, in which two near-infrared (NIR) fluorophores were conjugated via a flexible and acid liable linkage. While the fluorescence of this probe is quenched due to intramolecular dimeric aggregate under neutral environment, the cleavage of pH liable linkage with the concomitant disruption of aggregates in acidic tumor microenvironment results in a remarkable fluorescence enhancement. This probe not only visualized the primary tumors with high target to background (T/B) signal ratio in vivo, but also revealed the correlation between the M.P. and acidosis distribution pattern in tumor. While the acidosis locate dispersedly at tumor periphery in highly metastatic tumor, it distribute more widely in lowly metastatic tumor and the acidification degree increases substantially from the margin to core areas. This pH activatable NIR fluorescent probe holds the potential to evaluate the M.P., monitor the therapeutic response and predict the prognosis by delineating acidosis in tumors.Metastasis is an extremely complex disease that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and colonize the dormant organs.1 Because of the small volume, dispersal distribution nature and genetic heterogeneity of the metastases as well as the limited sensitivity and spatial resolution of the clinical imaging technologies, it is very difficult to detect and eliminate these metastatic cells in time, which results in organ failure and causes 90% of human cancer deaths.2 Therefore, monitoring the metastatic symptom and offering timely treatment are crucially important to reduce the metastasisassociated mortality. Metastatic potential (M.P.) defined as a tendency of a primary tumor to colonize in a distant organ is determined by gene expression signature of cancer cells 3 as well as the tumor microenvironment (TME).4 Like all predictive endeavors, the accurate determination of M.P. is a daunting task. For example, while tumors such as small cell lung cancer and melanoma form secondary lesions with high frequency, glioblastoma multiforme or basal cell carcinoma remain locally invasive.5 Therefore, accurately measuring tumor M.P. provides a unique opportunity to understand the metastasis mechanism, improve the therapeutic efficacy and estimate the prognosis of metastatic cancer.As a universal characteristic of TME, solid tumors demonstrate higher intracellular pH (pH...
Breaking the barrier of 1,2 HOPO complexes with extremely emissive Eu-Cy-HOPO (overall quantum yield −30.2%) that displays two photon properties.
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