Abstract:A stable doxorubicin (DOX)-loaded stereocomplex micelle drug delivery system was developed via the stereocomplex interaction between enantiomeric 4-armed poly(ethylene glycol)–poly(D-lactide) and poly(ethylene glycol)–poly(L-lactide) to realize control drug release and improve tumor cell uptake for efficient cervical carcinoma therapy. All these DOX-loaded micelles including poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) exhibited appropria… Show more
“…As a result, tumor cell activity was decreased with the drug delivery system compared to non-loaded drug performance. Increased tumor inhibition rates were also exhibited by doxorubicin-loaded stereocomplex micelles [41] .…”
Section: Applicationsmentioning
confidence: 96%
“… Fig. 4 Schematic of design of doxorubicin-loaded stereocomplex micelle and administration to mouse subject [41] . Fig.…”
Section: Applicationsmentioning
confidence: 99%
“…Cervical carcinoma is a major causation of cancer-related deaths amongst females on a global scale [41] . Current treatment options, including chemotherapy, have proven success in clinic, however, patient complications from side effects are well-documented.…”
Polylactic acid (PLA) is a versatile biopolymer. PLA is synthesized with ease from abundant renewable resources and is biodegradable. PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine, cardiovascular implants, dental niches, drug carriers, orthopedic interventions, cancer therapy, skin and tendon healing, and lastly medical tools / equipment. PLA has demonstrated instrumental importance as a three-dimensionally (3D) printable biopolymer, which has further been bolstered by its role during the Coronavirus Disease of 2019 (Covid-19) global pandemic. As an abundant filament, PLA has created desperately needed personal protective equipment (PPE) and ventilator modifications. As polymer chemistry continues to advance, so too will the applications and continued efficacy of PLA-based modalities.
“…As a result, tumor cell activity was decreased with the drug delivery system compared to non-loaded drug performance. Increased tumor inhibition rates were also exhibited by doxorubicin-loaded stereocomplex micelles [41] .…”
Section: Applicationsmentioning
confidence: 96%
“… Fig. 4 Schematic of design of doxorubicin-loaded stereocomplex micelle and administration to mouse subject [41] . Fig.…”
Section: Applicationsmentioning
confidence: 99%
“…Cervical carcinoma is a major causation of cancer-related deaths amongst females on a global scale [41] . Current treatment options, including chemotherapy, have proven success in clinic, however, patient complications from side effects are well-documented.…”
Polylactic acid (PLA) is a versatile biopolymer. PLA is synthesized with ease from abundant renewable resources and is biodegradable. PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine, cardiovascular implants, dental niches, drug carriers, orthopedic interventions, cancer therapy, skin and tendon healing, and lastly medical tools / equipment. PLA has demonstrated instrumental importance as a three-dimensionally (3D) printable biopolymer, which has further been bolstered by its role during the Coronavirus Disease of 2019 (Covid-19) global pandemic. As an abundant filament, PLA has created desperately needed personal protective equipment (PPE) and ventilator modifications. As polymer chemistry continues to advance, so too will the applications and continued efficacy of PLA-based modalities.
“…Antitumor therapeutic effects of Pha@FPPC-mediated PDT at a light dosage of 90 J/cm 2 and drug dosage of 2 mg/kg were investigated by measuring tumor volume and survival period of C57/6J mice bearing B16-F10 melanoma in five groups (control, Pha@FPPC, Pha@PPC, FPPC, and Pha) (Figure 5B). 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.…”
Section: Resultsmentioning
confidence: 82%
“…As a result, on the one hand, it should be expected that Pha@FPPC could improve water-solubility and tumor cellular uptake of Pha and chidamide, and directionally release Pha in tumor sites by acid-triggering in a tumor’s slightly acidic environment, resulting in enhancing PDT antitumor efficacy of free Pha due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention) effect as micelle nanoparticles 21–23. On the other hand, chidamide segment in Pha@FPPC could not only exert its own antitumor effect as an HDACi, but also augment PDT antitumor efficiency of Pha probably due to prevention the potential relapse and metastasis via inhibiting the elevated activity of HDAC induced by PDT.…”
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.
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