Folate chitosan conjugated doxorubicin and pyropheophorbide acid nanoparticles (FCDP–NPs) for enhance photodynamic therapy

Li, Wenting; Tan, Ge; Zhang, Hongyue; Wang, Zhiqiang; Jin, Yingxue

doi:10.1039/c7ra08757h

Cited by 16 publications

(8 citation statements)

References 49 publications

(45 reference statements)

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“…45 nm in size (Figure 1B, Figure S5). The hydrodynamic ( HD ) size was measured to be 5.76 ± 0.56 nm (Figure 1C) , a little larger than the size from TEM, this might be due to the HDs that corresponds to the core and the swollen corona of nanoparticles 35, 50, 51 . In addition, red - shift of Soret and Q bands in absorption spectra after modification suggested that Pa molecule in adducts might be contributed to form nanodot morphology via π - π stacking (Figure 1D).…”

Section: Resultsmentioning

confidence: 87%

Ultra-small Pyropheophorbide-a Nanodots for Near-infrared Fluorescence/Photoacoustic Imaging-guided Photodynamic Therapy

Siwawannapong¹,

Zhang²,

Lei³

et al. 2020

Theranostics

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Rationale: Nanoparticles (NPs) that are rapidly eliminated from the body offer great potential in clinical test. Renal excretion of small particles is preferable over other clearance pathways to minimize potential toxicity. Thus, there is a significant demand to prepare ultra-small theranostic agents with renal clearance behaviors.Method: In this work, we report a facile method to prepare NPs with ultra-small size that show renal clearable behavior for imaging-guided photodynamic therapy (PDT). Pyropheophorbide-a (Pa), a deep red photosensitizer was functionalized with polyethylene glycol (PEG) to obtain Pa-PEG. The prepared NPs formed ultra-small nanodots in aqueous solution and showed red-shifted absorbance that enabling efficient singlet oxygen generation upon light irradiation.Results: In vitro studies revealed good photodynamic therapy (PDT) effect of these Pa-PEG nanodots. Most of the cancer cells incubated with Pa-PEG nanodots were destroyed after being exposed to the irradiated light. Utilizing the optical properties of such Pa-PEG nanodots, in vivo photoacoustic (PA) and fluorescence (FL) imaging techniques were used to assess the optimal time for PDT treatment after intravenous (i.v.) injection of the nanodots. As monitored by the PA/FL dual-modal imaging, the nanodots could accumulate at the tumor site and reach the maximum concentration at 8 h post injection. Finally, the tumors on mice treated with Pa-PEG nanodots were effectively inhibited by PDT treatment. Moreover, Pa-PEG nanodots showed high PA/FL signals in kidneys implying these ultra-small nanodots could be excreted out of the body via renal clearance.Conclusion: We demonstrated the excellent properties of Pa-PEG nanodots that can be an in vivo imaging-guided PDT agent with renal clearable behavior for potential future clinical translation.

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Section: Resultsmentioning

confidence: 87%

Ultra-small Pyropheophorbide-a Nanodots for Near-infrared Fluorescence/Photoacoustic Imaging-guided Photodynamic Therapy

Siwawannapong¹,

Zhang²,

Lei³

et al. 2020

Theranostics

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“…It was noted that Cs-FA has abundant hydroxyl groups and can interact with the Si–O bond of the silicon layer. The preparation of PPa-APTES and Cs-FA was according to the literature, , as shown in Figure S1 (Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…The Cs-FA was prepared according to a previous report. 40 Briefly, 300 mg of folic acid was completely dissolved in 10 mL of DMSO, and 200 mg of DCC, 200 mg of NHS, and 0.5 mL of trimethylamine were added and stirred at 30 °C overnight. The by-products were removed by filtration and dropped into a cold 30% acetone diethyl ether solution to obtain a yellow precipitate, then filtered, and washed several times with anhydrous diethyl ether and dried in vacuum.…”

Section: ■ Conclusionmentioning

confidence: 99%

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Near-Infrared Light-Initiated Upconversion Nanoplatform with Tumor Microenvironment Responsiveness for Improved Photodynamic Therapy

Zhang

Wang

et al. 2020

ACS Appl. Bio Mater.

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Photodynamic therapy (PDT) is inflowing the mainstream of the cancer treatments, yet the shallow light penetration, thermal damage to normal cells, poor tumor targeting, and skin phototoxicity compromised the PDT efficacy. This paper designed and prepared an upconversion nanoplatform that could effectively convert 808 nm NIR light to red and green light emission, both of which could excite photosensitizers and exert the PDT curative effects. A thin layer of mesoporous silica covering core− shell nanostructure NaGdF 4 :Yb,Er@NaGdF 4 :Yb,Nd upconversion nanoparticles was prepared as the carrier to load the photosensitizer pyropheophorbide-a (PPa), which could be excited by green and red light simultaneously and produce high singlet oxygen ( 1 O 2 ) quantum yield (79.1%). Meanwhile, the chemotherapy drug doxorubicin (DOX) was absorbed in the pores of the SiO 2 layer to improve the therapeutic effect, and the folic acid-coupled chitosan (Cs-FA) was modified on the surface of the SiO 2 layer to obtain the targeting and biocompatible UCNP@SiO 2 /PPa&DOX@Cs-FA nanoplatform. The physically adsorbed DOX in the pore channel could be released slowly under faintly acidic or GSH stimuli (84% release of DOX after 16 h), suggesting that the nanoplatform was responsive to the tumor microenvironment. In vitro experiments showed that the combined treatment of PDT and DOX was superior to that of PDT alone or DOX chemotherapy alone, implying a synergistic therapeutic effect. The morphological changes and dye staining research of HeLa cells were consistent with the MTT assay. Therefore, this research provided a strategy for the development of an efficient and safe multifunctional cancer treatment nanoplatform integrating low-intensity light excitation, slow release, targeting, photodynamic therapy, and chemotherapy.

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“…To verify that the production of intracellular singlet oxygen is the main way to induce the cells death, we used 2,7dichlorofluorescin diacetate (DCFH-DA) to observe the generation of singlet oxygen after GFFP-TPPa incubation and laser irradiation. 48 DCFH-DA is a high specific fluorescent probe for 1 O 2 , which could be oxidized by 1 O 2 and emit green fluorescence to allow insitu confirmation of 1 O 2 . After HeLa cells were incubated with GFFP-TPPa (PPa concentration: 2 μg/mL) for 2 h, we added DCFH-DA into the cell and observed their emission by FIM.…”

Section: Acs Applied Bio Materialsmentioning

confidence: 99%

Fabrication of Multitargeting and pH-Regulated Nanocomposites for Antitumor Photodynamic Therapy Based on Triphenylphosphine and Graphene Oxide

Zhang

Qin

et al. 2019

ACS Appl. Bio Mater.

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Targeted delivery of photosensitizer for antitumor photodynamic therapy has received much attention recently. In this research, a multitargeting graphene oxide (GO) nanosystem (GFFP-TPPa) was fabricated based on the magnetically targeted nano-Fe 3 O 4 , active targeted folic acid (FA), and mitochondria-targeted triphenylphosphine, aiming to provide an effective drug delivery system of photosensitizer for improved photodynamic therapy against human tumor. The effective photosensitizer release from GFFP-TPPa under mild acidic pH condition (such as tumor microenvironment) suggested our designed nanosystem could reduce cutaneous phototoxicity of nanoparticles (NPs) in normal cells environment, which was further verified by the observation that the fluorescence of GFFP-TPPa was significantly quenched compared with free PPa. Research of cellular morphological variation, uptaking test, and intracellular single oxygen detection has validated the effectiveness of GFFP-TPPa NPs against tumor cells and potential fluorescence imaging function. Moreover, GFFP-TPPa NPs have excellent superparamagnetic properties and FA-targeted property of NPs, which was verified by the tumor cellular uptake of GFFP-TPPa. Finally, the precise deliver of photosensitizer to mitochondria has been proved by Mito-Tracker Green organelle localization. Our research indicated that the fabricated nanosystem could be applied conveniently for PDT based on multitargetability.

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Folate chitosan conjugated doxorubicin and pyropheophorbide acid nanoparticles (FCDP–NPs) for enhance photodynamic therapy

Abstract: Newly prepared folate chitosan conjugated doxorubicin and pyropheophorbide acid nanoparticles (FCDP–NPs) showed remarkable PDT activity against HepG2 cells.

Cited by 16 publications

References 49 publications

Ultra-small Pyropheophorbide-a Nanodots for Near-infrared Fluorescence/Photoacoustic Imaging-guided Photodynamic Therapy

Ultra-small Pyropheophorbide-a Nanodots for Near-infrared Fluorescence/Photoacoustic Imaging-guided Photodynamic Therapy

Near-Infrared Light-Initiated Upconversion Nanoplatform with Tumor Microenvironment Responsiveness for Improved Photodynamic Therapy

Fabrication of Multitargeting and pH-Regulated Nanocomposites for Antitumor Photodynamic Therapy Based on Triphenylphosphine and Graphene Oxide

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