Abstract:Herein, folic acid (FA) conjugated Poly(d,l-lactide-co-glycolide) (PLGA)-lipid composites (FA-PL) were developed as nanocarriers for the targeted delivery of insoluble anti-cancer drug paclitaxel (PTX), resulting FA-PLP nanoparticles. Furthermore, 131I, as a radioactive tracer, was used to label FA-PLP nanoparticles (FA-PLP-131I) to evaluate their cell uptake activity, in vivo blood circulation, and biodistribution. The FA-PLP-131I nanoparticles had a spherical morphology with great stability, a narrow size di… Show more
“…In addition, Pha@FPPC micelles had lower dark cytotoxicity against B16-F10 and A2780 cells and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. More encouragingly, Pha@FPPC not only significantly strengthened the PDT antitumor efficacy on B16-F10-bearing mice of free Pha due to both its FA-mediated tumor-targeting17–19 and EPR effect of tumor as micelle nanoparticles21–23 but also remarkably prevented pulmonary metastasis of mice melanoma due to chidamide segment as a HDACi, resulting in a significant synergistic antitumor effect of photosensitizer and HDACi. All in all, as a new modality of photodynamic therapy, folate-mediated and acid-activated chidamide-grafted drug-delivery polymer micelles, Pha@FPPC indeed have great potential to inhibit tumor metastasis and relapse in clinical photodynamic treatment.…”
Section: Resultsmentioning
confidence: 87%
“…Compared with the control group, on day 3 after PDT, Pha@FPPC, and Pha@PPC groups initiated significant difference ( P <0.01 and P <0.05, respectively), while other groups indicated significant difference on day 4–6 in variety, demonstrating encapsulation of Pha into drug-delivery carrier FPPC could significantly enhance the PDT antitumor effect of Pha in vivo due to EPR effect of tumor as micelle nanoparticles 21–23. On day 7 after PDT, the destiny Pha@FPPC group showed a significant difference compared with every other group, indicating the advantage of folate-targeting strategy in retarding tumor proliferation due to its FA-mediated tumor targeting 17–19. Additionally, compared with the control group, the FPPC group showed significant difference on day 5 after PDT, hinting the antitumor effect of chidamide bound to the polymer vehicle.Figure 5PDT antitumor efficacy of Pha@FPPC on mice bearing B16-F10 melanoma in vivo. Notes: ( A ) Mice bearing B16-F10 melanoma irradiated by the diode laser at 660 nm with a light dosage of 90 J/cm 2 at 45 mins after intravenous administration with a drug dosage of 2 mg/kg; ( B ) tumor growth curve (*Represented the differences of control group vs every other group, and # represented the differences of Pha@FPPC vs every other group, * P, # P <0.05, ** P, ## P <0.01 and *** P, P <0.001); ( C ) survival curves of C57BL/6J (control vs Pha@FPPC, * P =0.0127; control vs Pha@PPC, * P =0.0499; Pha@FPPC vs Pha, # P =0.0471; Pha@FPPC vs FPPC, & P =0.0364), the data were shown as the mean ± standard deviation, n =5; ( D ) the posteroanterior photographs of lung tissues with metastatic nodules of the first dead mice bearing B16-F10 melanoma in each group after PDT.…”
Section: Resultsmentioning
confidence: 93%
“…After tumor cellular uptake of the Pha@FPPC micelles through FA-receptor-mediated endocytosis,17–19 endosomes evolve into lysosome due to the proton pump effects in the membrane of endosomes 20. Therefore, pH value of the lysosome finally could reach to 5.2 or even lower, and pH-responsive segment polymer poly(aspartic acid) (PAsp) was to turn to hydrophilicity from hydrophobicity in neutral solution, and Pha molecules were then directionally released in the lysosome from the micelles.…”
Background:
Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic.
Purpose:
In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-
b
-poly(aspartic acid) (PEG-
b
-PAsp) grafted folate (FA-PEG-
b
-PAsp) to obtain the block polymer folate polyethylene glycol-
b
-poly(asparaginyl-chidamide) (FA-PEG-
b
-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice.
Methods:
Model photosensitizer pyropheophorbide-
a
(Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-
b
-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis.
Results:
With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi.
Conclusion:
As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.
“…In addition, Pha@FPPC micelles had lower dark cytotoxicity against B16-F10 and A2780 cells and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. More encouragingly, Pha@FPPC not only significantly strengthened the PDT antitumor efficacy on B16-F10-bearing mice of free Pha due to both its FA-mediated tumor-targeting17–19 and EPR effect of tumor as micelle nanoparticles21–23 but also remarkably prevented pulmonary metastasis of mice melanoma due to chidamide segment as a HDACi, resulting in a significant synergistic antitumor effect of photosensitizer and HDACi. All in all, as a new modality of photodynamic therapy, folate-mediated and acid-activated chidamide-grafted drug-delivery polymer micelles, Pha@FPPC indeed have great potential to inhibit tumor metastasis and relapse in clinical photodynamic treatment.…”
Section: Resultsmentioning
confidence: 87%
“…Compared with the control group, on day 3 after PDT, Pha@FPPC, and Pha@PPC groups initiated significant difference ( P <0.01 and P <0.05, respectively), while other groups indicated significant difference on day 4–6 in variety, demonstrating encapsulation of Pha into drug-delivery carrier FPPC could significantly enhance the PDT antitumor effect of Pha in vivo due to EPR effect of tumor as micelle nanoparticles 21–23. On day 7 after PDT, the destiny Pha@FPPC group showed a significant difference compared with every other group, indicating the advantage of folate-targeting strategy in retarding tumor proliferation due to its FA-mediated tumor targeting 17–19. Additionally, compared with the control group, the FPPC group showed significant difference on day 5 after PDT, hinting the antitumor effect of chidamide bound to the polymer vehicle.Figure 5PDT antitumor efficacy of Pha@FPPC on mice bearing B16-F10 melanoma in vivo. Notes: ( A ) Mice bearing B16-F10 melanoma irradiated by the diode laser at 660 nm with a light dosage of 90 J/cm 2 at 45 mins after intravenous administration with a drug dosage of 2 mg/kg; ( B ) tumor growth curve (*Represented the differences of control group vs every other group, and # represented the differences of Pha@FPPC vs every other group, * P, # P <0.05, ** P, ## P <0.01 and *** P, P <0.001); ( C ) survival curves of C57BL/6J (control vs Pha@FPPC, * P =0.0127; control vs Pha@PPC, * P =0.0499; Pha@FPPC vs Pha, # P =0.0471; Pha@FPPC vs FPPC, & P =0.0364), the data were shown as the mean ± standard deviation, n =5; ( D ) the posteroanterior photographs of lung tissues with metastatic nodules of the first dead mice bearing B16-F10 melanoma in each group after PDT.…”
Section: Resultsmentioning
confidence: 93%
“…After tumor cellular uptake of the Pha@FPPC micelles through FA-receptor-mediated endocytosis,17–19 endosomes evolve into lysosome due to the proton pump effects in the membrane of endosomes 20. Therefore, pH value of the lysosome finally could reach to 5.2 or even lower, and pH-responsive segment polymer poly(aspartic acid) (PAsp) was to turn to hydrophilicity from hydrophobicity in neutral solution, and Pha molecules were then directionally released in the lysosome from the micelles.…”
Background:
Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic.
Purpose:
In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-
b
-poly(aspartic acid) (PEG-
b
-PAsp) grafted folate (FA-PEG-
b
-PAsp) to obtain the block polymer folate polyethylene glycol-
b
-poly(asparaginyl-chidamide) (FA-PEG-
b
-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice.
Methods:
Model photosensitizer pyropheophorbide-
a
(Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-
b
-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis.
Results:
With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi.
Conclusion:
As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.
“…5b ). The results demonstrated that the conjugated FA facilitated the nanoparticles to target the FA receptors on tumor cells and thus enhance FA-IHA NPs cell uptake [ 39 , 40 , 41 ]. Fig.…”
Herein, a tumor-targeted multifunctional theranostic agent was synthetized using a facile method, combining four clinically approved materials: artesunate (Arte), human serum albumin (HSA), folic acid (FA), and indocyanine green (ICG). The obtained nanocomposites (FA-IHA NPs) showed an excellent photo- and physiological stability. The ICG in the FA-IHA NPs was used not only for near infrared (NIR) fluorescence imaging, but also for photothermal and photodynamic (PTT-PDT) therapy under a single NIR irradiation. In addition, the NIR irradiation (808 nm, 1 W/cm2) could trigger Arte release that showed enhanced chemotherapeutic effect. Through fluorescence imaging, the cell uptake and tumor accumulation of FA-IHA NPs were observed in vitro and in vivo, analyzed by confocal microscopy and NIR fluorescence imaging in tumor xenograft mice. Based on the diagnostic results, FA-IHA NPs at 24 h post injection and combined with NIR irradiation (808 nm, 1 W/cm2) could efficiently suppress tumor growth through a photo-chemo combination therapy, with no tumor recurrence in vitro and in vivo. The obtained results suggested that FA-IHA NPs are promising photo-chemo theranostic agents for future clinical translation.Electronic supplementary materialThe online version of this article (10.1186/s11671-018-2700-5) contains supplementary material, which is available to authorized users.
“…As melanoma is characterized by rapid progression, poor prognosis, and high mortality, various treatments have been developed. Chemotherapy is the optimal treatment for melanoma, although it results in low bioavailability, side effects, poor tumor selectivity, and dose-limiting systemic toxicity (2). In addition, uncontrolled melanoma cell proliferation results in resistance to conventional treatment approaches.…”
Chamaejasmin B (CHB), a natural biflavone isolated from Stellera chamaejasme L., has been reported to exhibit anti-cancer properties; however, its effect in melanoma cells is not clear. Here, we aimed to investigate the anticancer effect of CHB in mouse melanoma B16F0 and B16F10 cells. We found that CHB significantly suppressed cell proliferation and promoted cell cycle arrest at G0/G1 phase in B16F0 cells; it also induced cell differentiation and increased melanin content by increasing tyrosinase (TYR) activity and mRNA levels of melanogenesis-related genes in B16F0 cells. Meanwhile, wound closure, invasion, and migration of B16F0 and B16F10 cells were dramatically inhibited. Moreover, CHB significantly increased ROS levels and decreased Ψ m, resulting in B16F0 and B16F10 cell apoptosis. Finally, in vivo studies showed that CHB inhibited tumor growth and induced tumor apoptosis in a mouse xenograft model of murine melanoma B16F0 and B16F10 cells. Overall, CHB decreases malignant characteristics and may be a promising therapeutic agent for malignant melanoma cells via multiple signaling pathways.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.