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1.
Yakugaku Zasshi ; 141(3): 327-332, 2021.
Article in Japanese | MEDLINE | ID: mdl-33642499

ABSTRACT

Controlled drug release in response to light irradiation is an important technique for focusing drug elution to specific sites and reducing the side effects of drugs in normal tissue. In one example, we used double-stranded DNA to modify gold nanorods. When the gold nanorods were heated by irradiation with near-infrared light, single-stranded DNA was released. Thus, we successfully prepared a controlled release system that responds to near-infrared irradiation by combining heat-labile linkers such as double-stranded DNA. However, the drug-loading capacity on the surface of the nanoparticles was limited. To improve the loading efficiency, we encapsulated gold nanorods in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, where PLGA acted as a drug payload. When the gold nanorod-containing PLGA nanoparticles were irradiated with a near-infrared laser, the PLGA nanoparticles were destroyed and significant drug release was observed. In another example, silver nanoplates were used as a near-infrared responsive photothermal nanodevice. Silver nanoparticles show antimicrobial activity that we expected could be controlled by light irradiation. First, we coated the silver nanoplates with gold atoms to mask the antimicrobial activity. When the gold-coated silver nanoplates were irradiated with a near-infrared pulsed laser, the shape of the silver nanoplates changed from plate-like to spherical, and silver ions were released. As a result, the antibacterial activity of the silver nanoplates was recovered. In this review, we outline examples of controlled release systems that respond to light irradiation. We believe that this review will contribute to improving the efficiency and safety of chemotherapy.


Subject(s)
Drug Liberation/radiation effects , Gold , Infrared Rays , Metal Nanoparticles , Nanotubes , Animals , Anti-Infective Agents , DNA , Gold/pharmacology , Gold/radiation effects , Hot Temperature , Humans , Metal Nanoparticles/radiation effects , Mice , Nanotubes/radiation effects , Polylactic Acid-Polyglycolic Acid Copolymer/radiation effects , Silver/pharmacology , Silver/radiation effects
2.
ACS Appl Mater Interfaces ; 12(51): 57290-57301, 2020 Dec 23.
Article in English | MEDLINE | ID: mdl-33231083

ABSTRACT

Our exploration of multimodal nanoprobes aims to combine photoacoustic (PA) imaging, 19F magnetic resonance (MR), and fluorescence (FL) imaging, which offers complementary advantages such as high spatial resolution, unlimited penetration, and high sensitivity to enable more refined images for accurate tumor diagnoses. In this research, perfluorocarbons (PFCs) and indocyanine green (ICG) are encapsulated by poly(lactic-co-glycolic acid) (PLGA) for intravital 19F MR/FL/PA tri-modal imaging-guided photothermal therapy. Then, it is coated with an A549 cancer cell membrane (AM) to fabricate versatile theranostic nanoprobes (AM-PP@ICGNPs). After systemic administration, FLI reveals time-dependent tumor homing of NPs with high sensitivity, 19F MRI provides tumor localization of NPs without background signal interference, and PAI illustrates the detailed distribution of NPs inside the tumor with high spatial resolution. What is more, AM-PP@ICGNPs accumulated in the tumor area exhibit a prominent photothermal effect (48.4 °C) under near infrared (NIR) laser irradiation and realize an enhanced antitumor response in vivo. These benefits, in combination with the excellent biocompatibility, make AM-PP@ICGNPs a potential theranostic nanoagent for accurate tumor localization and ultimately achieve superior cancer therapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Cell Membrane/chemistry , Nanoparticles/therapeutic use , Neoplasms/drug therapy , A549 Cells , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Fluorine/chemistry , Fluorocarbons/chemistry , Fluorocarbons/radiation effects , Fluorocarbons/therapeutic use , Humans , Indocyanine Green/chemistry , Indocyanine Green/radiation effects , Indocyanine Green/therapeutic use , Infrared Rays , Magnetic Resonance Imaging , Male , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/radiation effects , Neoplasms/diagnostic imaging , Optical Imaging , Photoacoustic Techniques , Photothermal Therapy/methods , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/radiation effects , Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use , Theranostic Nanomedicine/methods , Xenograft Model Antitumor Assays
3.
Drug Dev Ind Pharm ; 46(4): 659-672, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32208984

ABSTRACT

Objective: In vitro, optimization, characterization, and cytotoxic studies of NAR nanoparticles (NPs) to against pancreatic cancer.Method: The sonication tailored Naringenin (NARG)-loaded poly (lactide-co-glycolic acid) (PLGA) NPs was fabricated for potential cytotoxic effect against pancreatic cancer. NARG NPs were prepared by emulsion-diffusion evaporation technique applying BoxBehnken experimental design based on three-level and three-factors. The effect of independent variables surfactant concentration (X1), polymer concentration (X2), and sonication time (X3) were studied on responses particle size (Y1), and drug release % (Y2). NPs characterized for particles size and size distribution, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimeter (DSC), and X-ray diffraction (XRD) studies. Further, the studies was fitted to various drug release kinetic model and cytotoxicity evaluated in vitro.Results: The nanosized particles were spherical, uniform with an average size of 150.45 ± 12.45 nm, PDI value 0.132 ± 0.026, zeta potential -20.5 ± 2.5 mV, and cumulative percentage release 85.67 ± 6.23%. In vitro release of NARG from nanoparticle evaluated initially burst followed by sustained release behavior. The Higuchi was best fitted model to drug release from NARG NPs. The cytotoxicity study of NARG NPs apparently showed higher cytotoxic effect over free NARG (p < 0.05). The stability study of optimized formulation revealed no significant physico-chemical changes during 3 months.Conclusions: Thus, NARG-loaded NPs gave ameliorated anticancer effect over plain NARG.


Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Drug Compounding/methods , Flavanones/administration & dosage , Pancreatic Neoplasms/drug therapy , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Chemistry, Pharmaceutical , Drug Carriers/radiation effects , Drug Liberation/radiation effects , Drug Screening Assays, Antitumor , Drug Stability , Flavanones/pharmacokinetics , Humans , Nanoparticles/chemistry , Nanoparticles/radiation effects , Pancreatic Neoplasms/pathology , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/radiation effects , Sonication
4.
Int J Pharm ; 572: 118733, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31689481

ABSTRACT

Brain delivery of drugs by nanoparticles is a promising strategy that could open up new possibilities for the chemotherapy of brain tumors. As demonstrated in previous studies, the loading of doxorubicin in poly(lactide-co-glycolide) nanoparticles coated with poloxamer 188 (Dox-PLGA) enabled the brain delivery of this cytostatic that normally cannot penetrate across the blood-brain barrier in free form. The Dox-PLGA nanoparticles produced a very considerable anti-tumor effect against the intracranial 101.8 glioblastoma in rats, thus representing a promising candidate for the chemotherapy of brain tumors that warrants clinical evaluation. The objective of the present study, therefore, was the optimization of the Dox-PLGA formulation and the development of a pilot scale manufacturing process. Optimization of the preparation procedure involved the alteration of the technological parameters such as replacement of the particle stabilizer PVA 30-70 kDa with a presumably safer low molecular mass PVA 9-10 kDa as well as the modification of the external emulsion medium and the homogenization conditions. The optimized procedure enabled an increase of the encapsulation efficiency from 66% to >90% and reduction of the nanoparticle size from 250 nm to 110 nm thus enabling the sterilization by membrane filtration. The pilot scale process was characterized by an excellent reproducibility with very low inter-batch variations. The in vitro hematotoxicity of the nanoparticles was negligible at therapeutically relevant concentrations. The anti-tumor efficacy of the optimized formulation and the ability of the nanoparticles to penetrate into the intracranial tumor and normal brain tissue were confirmed by in vivo experiments.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Brain Neoplasms/drug therapy , Doxorubicin/administration & dosage , Glioblastoma/drug therapy , Nanoparticles/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage , Animals , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/radiation effects , Doxorubicin/chemistry , Doxorubicin/radiation effects , Drug Development , Drug Stability , Male , Nanoparticles/chemistry , Nanoparticles/radiation effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/radiation effects , Rats, Wistar , Sterilization
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