Poly(ethylene glycol)-block-poly(&amp;epsilon;-caprolactone)&amp;ndash; and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Li, Li; He, Xin; Su, Hua; Zhou, Dongxu; Song, Hongmei; Jiang, Xuehua

doi:10.2147/ijn.s75186

Cited by 23 publications

(8 citation statements)

References 35 publications

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“…26 On the other hand, PEG-modified liposomes, like PTX–BSA-liposomes, have a hydration layer on the surface of the liposome, which results in inhibiting cellular uptake. 27,28 In the present study, confocal images clearly showed that DNSA–BSA-liposomes are taken up by AsPC-1 cells in the form of intact BSA-liposomes (Figure 4). In addition, the pretreatment of cytochalasin D (an inhibitor of micropinocytosis pathway) resulted in significant inhibition of the cellular uptake of Cy5-labeled BSA-liposomes by AsPC-1 cells but a filipin pretreatment (an inhibitor of the caveolae-mediated pathway) did not (Figure S5).…”

Section: Discussionsupporting

confidence: 65%

Preparation, Characterization, and in Vitro/in Vivo Evaluation of Paclitaxel-Bound Albumin-Encapsulated Liposomes for the Treatment of Pancreatic Cancer

Okamoto¹,

Taguchi

Saeedi³

et al. 2019

ACS Omega

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Paclitaxel (PTX)-loaded liposomes were developed with the goal of enhancing the effects of cancer treatment. Although loading substances into the lipid membrane of liposome cause some destabilization of the lipid membrane, PTX was nearly exclusively embedded in the lipid membrane of liposomes, due to its low water solubility. Hydrophobic drugs can be encapsulated into the inner core of bovine serum albumin (BSA)-encapsulated liposomes (BSA-liposome) via noncovalent binding to albumin. Since PTX is able to noncovalently bind to albumin, we attempted to prepare PTX-loaded BSA-liposome (PTX–BSA-liposome). The amount of PTX loaded in the BSA-liposome could be increased substantially by using ethanol, since ethanol increases PTX solubility in BSA solutions via prompting the binding PTX to BSA. On the basis of the results of transmission electron microscopy and small-angle X-ray scattering, PTX–BSA-liposome formed unilamellar vesicles that were spherical in shape and the PTX was encapsulated into the inner aqueous core of the liposome as a form of PTX–BSA complex. In addition, the PTX–BSA-liposome, as well as nab-PTX, showed cytotoxicity against human pancreatic cancer cells, AsPC-1 cells, in a PTX concentration-dependent manner. The in vivo antitumor effect of PTX–BSA-liposomes was also observed in a mouse model that had been subcutaneously inoculated with pancreatic cancer cells by virtue of its high accumulation at the tumor site via the enhanced permeability retention effect. These results suggest that PTX–BSA-liposomes have the potential for serving as a novel PTX preparation method for the treatment of pancreatic cancer.

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Section: Discussionsupporting

confidence: 65%

Preparation, Characterization, and in Vitro/in Vivo Evaluation of Paclitaxel-Bound Albumin-Encapsulated Liposomes for the Treatment of Pancreatic Cancer

Okamoto¹,

Taguchi

Saeedi³

et al. 2019

ACS Omega

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“…This might be due to the fact that the free PTX could be easily internalized by passive diffusion, whereas PTX in the NPs is gradually released into the cytoplasm and therefore the cytotoxicity is cumulative over time in vitro 48 - 50 . However, when applied in vivo , free PTX may cause serious side effect, whereas the targeted NPs would deliver PTX to the tumor site specifically 50 , 51 . Surprisingly, the IC50 was found to be consistent with the total uptake not only for 24 h but also for 48 h, where a lower IC50 matched a higher total uptake.…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer

Xing¹,

Shi²,

Zheng³

et al. 2016

Theranostics

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Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer.

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“…Novel stealth nanoparticles of poly(ethylene glycol)-block-poly(ε-caprolactone)-and phospholipid-based were applied as PTX nanocarriers showing enhanced therapeutic effectiveness on murine breast cancer due to the improved intracellular drug delivery [ 301 ]. Additionally, PTX was encapsulated in novel lipid–polymer hybrid drug nanocarriers consisting of folate (FA) modified lipid-shell-1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N -[methoxy (polyethylene glycol)-2000] DSPE-PEG2000 (as lipid-shell), and PCL-PEG-PCL (as self-assembled core) (FLPNPs) expressing controlled and targeted delivery of PTX inhibiting tumour growth [ 302 ].…”

Section: Types Of Nanocarriersmentioning

confidence: 99%

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

Sıafaka

Okur

Karavas

et al. 2016

IJMS

160

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Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

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Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

Cited by 23 publications

References 35 publications

Preparation, Characterization, and in Vitro/in Vivo Evaluation of Paclitaxel-Bound Albumin-Encapsulated Liposomes for the Treatment of Pancreatic Cancer

Preparation, Characterization, and in Vitro/in Vivo Evaluation of Paclitaxel-Bound Albumin-Encapsulated Liposomes for the Treatment of Pancreatic Cancer

Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

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