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The integration of diagnosis and therapy is an effective way to improve therapeutic effects for cancer patients, which has acquired widely attentions from researchers. Herein, a multifunctional drug-loaded nanosystem (F/A-PLGA@DOX/SPIO) has been designed and synthesized to reduce the side effects of traditional chemotherapy drugs and realize simultaneous tumor diagnosis and treatment. The surface modification of folic acid (FA) and activatable cell-penetrating peptide (ACPP) endows the nanosystem with excellent cancer targeting capabilities, thus reducing toxicity to normal organs. Besides, the F/A-PLGA@DOX/SPIO nanosystem can serve as an excellent magnetic resonance imaging (MRI) T2-negative contrast agent. More importantly, according to in vitro experiments, the F/A-PLGA@DOX/SPIO nanosystem can promote the overproduction of reactive oxygen species (ROS) within A549 lung cancer cells, inducing cell apoptosis, greatly enhancing the antineoplastic effect. Furthermore, with the help of MRI technology, the targeting imaging of the F/A-PLGA@DOX/SPIO nanosystem within tumors and the dynamic monitoring of medicine efficacy can be realized. Therefore, this study provided a multifunctional drug-loaded F/A-PLGA@DOX/SPIO targeted nanosystem for magnetic resonance molecular imaging-guided theranostics, which has excellent potential for the application in tumor diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of novel anticancer drugs to enhance the cancer targeting effects and biocompatibility, and decrease toxic side effects. Camptothecin (CPT) demonstrated strong anticancer activity in clinical trials but also notorious adverse effects. In this study, we presented a smart targeted delivery system (Biotin-ss-CPT) that consists of cancer-targeted moiety (biotin), a cleavable disulfide linker (S-S bond) and the active drug CPT. Biotin-ss-CPT was found to exhibit potent effects on the migration of cancer cells and induced apoptosis by induction of ROS-mediated mitochondrial dysfunction and perturbation of GSH/GPXs system, as well as activation of caspases. In vivo tumor suppression investigation including toxicity evaluation and pathology analysis, accompanied by MR images showed that Biotin-ss-CPT can be recognized specifically and selectively and taken up preferentially by cancers cells, followed by localization and accumulation effectively in tumor site, then released CPT by biological response to achieve high therapeutic effect and remarkably reduced the side effects that free CPT caused, such as liver damage, renal injury, and weight loss to realize precise cancer therapy. Taken together, our results suggest that biotinylation and bioresponsive functionalization of anticancer drugs could be a good way for the discovery of next-generation cancer therapeutics. [ABSTRACT FROM AUTHOR]

Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs) can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs exhibit higher anticancer activity against HepG2 cells, while the larger sized (80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS overproduction in cancer cells, leading to DNA damage and p53 phosphorylation, consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious toxicity in major organs of tumor-bearing nude mice. Taken together, these results verify the size effects of MSNs nanosystem for precise cancer therapy. [ABSTRACT FROM AUTHOR]

The integration of diagnosis and therapy is an effective way to improve therapeutic effects for cancer patients, which has acquired widely attentions from researchers. Herein, a multifunctional drug-loaded nanosystem (F/A-PLGA@DOX/SPIO) has been designed and synthesized to reduce the side effects of traditional chemotherapy drugs and realize simultaneous tumor diagnosis and treatment. The surface modification of folic acid (FA) and activatable cell-penetrating peptide (ACPP) endows the nanosystem with excellent cancer targeting capabilities, thus reducing toxicity to normal organs. Besides, the F/A-PLGA@DOX/SPIO nanosystem can serve as an excellent magnetic resonance imaging (MRI) T2-negative contrast agent. More importantly, according to in vitro experiments, the F/A-PLGA@DOX/SPIO nanosystem can promote the overproduction of reactive oxygen species (ROS) within A549 lung cancer cells, inducing cell apoptosis, greatly enhancing the antineoplastic effect. Furthermore, with the help of MRI technology, the targeting imaging of the F/A-PLGA@DOX/SPIO nanosystem within tumors and the dynamic monitoring of medicine efficacy can be realized. Therefore, this study provided a multifunctional drug-loaded F/A-PLGA@DOX/SPIO targeted nanosystem for magnetic resonance molecular imaging-guided theranostics, which has excellent potential for the application in tumor diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of novel anticancer drugs to enhance the cancer targeting effects and biocompatibility, and decrease toxic side effects. Camptothecin (CPT) demonstrated strong anticancer activity in clinical trials but also notorious adverse effects. In this study, we presented a smart targeted delivery system (Biotin-ss-CPT) that consists of cancer-targeted moiety (biotin), a cleavable disulfide linker (S-S bond) and the active drug CPT. Biotin-ss-CPT was found to exhibit potent effects on the migration of cancer cells and induced apoptosis by induction of ROS-mediated mitochondrial dysfunction and perturbation of GSH/GPXs system, as well as activation of caspases. In vivo tumor suppression investigation including toxicity evaluation and pathology analysis, accompanied by MR images showed that Biotin-ss-CPT can be recognized specifically and selectively and taken up preferentially by cancers cells, followed by localization and accumulation effectively in tumor site, then released CPT by biological response to achieve high therapeutic effect and remarkably reduced the side effects that free CPT caused, such as liver damage, renal injury, and weight loss to realize precise cancer therapy. Taken together, our results suggest that biotinylation and bioresponsive functionalization of anticancer drugs could be a good way for the discovery of next-generation cancer therapeutics. [ABSTRACT FROM AUTHOR]

Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs) can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs exhibit higher anticancer activity against HepG2 cells, while the larger sized (80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS overproduction in cancer cells, leading to DNA damage and p53 phosphorylation, consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious toxicity in major organs of tumor-bearing nude mice. Taken together, these results verify the size effects of MSNs nanosystem for precise cancer therapy. [ABSTRACT FROM AUTHOR]