Polylactide-Based Block Copolymeric Micelles Loaded with Chlorin e6 for Photodynamic Therapy: <i>In Vitro</i> Evaluation in Monolayer and 3D Spheroid Models

Kumari, Preeti; Jain, Samyak; Ghosh, Balaram; Zorin, Vladimir; Biswas, Swati

doi:10.1021/acs.molpharmaceut.7b00548

Cited by 29 publications

(24 citation statements)

References 52 publications

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“…T820/Ce6 micelles could effectively keep Ce6 incorporated in the core during blood circulation, which was beneficial to avoid systemic toxicity resulting from rapid and nonspecific release of Ce6 from carriers. A similar release behavior was obtained previously . In the related work, a nanoformulation loading Ce6 in methoxy‐poly‐(ethylene glycol)‐poly( D,L ‐lactide) (mPEG‐PLA) copolymeric micelles was developed and the release of Ce6 also showed a prolonged manner.…”

Section: Resultssupporting

confidence: 82%

“…In the related work, a nanoformulation loading Ce6 in methoxy‐poly‐(ethylene glycol)‐poly( D,L ‐lactide) (mPEG‐PLA) copolymeric micelles was developed and the release of Ce6 also showed a prolonged manner. Compared with Ce6–mPEG–PLA micelles, T820/Ce6 micelles showed lower accumulative release amount and slower release rate in release profile of Ce6. For instances, at 24 h, the accumulative release amount of Ce6 from Ce6–mPEG–PLA micelles reached up to 60% which was much higher than that from T820/Ce6 micelles (47%), indicating the superiority of T820 micelles in firmly delivering Ce6 to tumor tissues by aid of EPR effect.…”

Section: Resultsmentioning

confidence: 89%

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Rational Design of IR820‐ and Ce6‐Based Versatile Micelle for Single NIR Laser–Induced Imaging and Dual‐Modal Phototherapy

Tian

Jiang

et al. 2018

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triggered by near-infrared (NIR) lightexcited photothermal agents [10] while PDT causes the cell death by photosensitizers generating highly cytotoxic reactive oxygen species (ROS) upon light excitation. [11][12][13] With distinct mechanisms of action, the integration of PTT and PDT into one nanoplatform holds great potential to achieve highly efficient cancer therapy. [14][15][16] However, in such combined therapy, two different excitation wavelengths are usually required for the activation of PTT and PDT, [17][18][19] leading to complicated treatment process and prolonged therapeutic time. Thus, it is highly desirable to design a nanoplatform with single NIR light-induced phototherapy.Although strategies of single-wavelength NIR light-mediated PTT/PDT combination therapy have been reported, photothermal agents commonly used in combined systems are inorganic nanomaterials, like gold nanostructures, [20][21][22] MoS 2 nanosheets, [23] black phosphorus nanosheets, [24] and black titania, [25] which show tedious preparation process, poor degradation, difficult excretion, and potential long-term toxicity. NIR organic dyes, which possess unique advantages of outstanding biodegradability and biocompatibility in contrast with inorganic photothermal agents, will be ideal alternatives. Especially, for new indocyanine green (IR820), a structural analog of indocyanine green (ICG), which has been approved by the Food and Drug Administration (FDA) in clinical use, [26][27][28] holds the suitable fluorescence, strong absorption in NIR region, and efficient light-thermal conversion. [29,30] Additionally, it is more stable and easily modified due to the meso-halogen in its chemical structure. Unfortunately, it differs from organic photodynamic agents in intrinsic excitation wavelength, bringing a great challenge to achieve single NIR laser-induced combinational phototherapy. Moreover, it suffers from short half-life in blood, rapid clearance from the body, and lack of specificity to target tumor area. [31,32] Chlorin e6 (Ce6), an FDA-approved second-generation photosensitizer, [33] is extensively used in PDT on account of its high singlet oxygen generation efficiency, [34] near-infrared light excitation allowing deep tissue penetration, and fluorescence imaging capability. [35,36] Despite these upsides, Ce6 has shortcomings including poor water solubility and nonspecific accumulation in tumor sites, [37] which largely compromise Phototherapy as a promising cancer diagnostic and therapeutic strategy has aroused extensive attention. However, single-wavelength near-infrared (NIR) light-triggered combinational treatment of photothermal therapy (PTT) and photodynamic therapy (PDT) is still a great challenge. Herein, a multifunctional micelle activated by a single-wavelength laser for simultaneous PTT and PDT as well as fluorescence imaging is developed. Briefly, new indocyanine green (IR820) is conjugated to d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via the linker 6-aminocaproic acid, and then, chlorin e6 (Ce6) is enc...

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 89%

Rational Design of IR820‐ and Ce6‐Based Versatile Micelle for Single NIR Laser–Induced Imaging and Dual‐Modal Phototherapy

Tian

Jiang

et al. 2018

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“…Finally, a significantly better PDT response in stroma-rich FaDu:MeWo 5:5 spheroids was obtained compared with FaDu homospheroids.Ce6. Contrary to mTHPC, Ce6 is more hydrophilic and penetrates more easily into spheroids [61,62,63]. Ce6 penetration in homospheroids requires 24 h, while in heterospheroids this process is accelerated and complete distribution is achieved at already 6 h. Similar to mTHPC, Ce6 possesses selectivity against FaDu tumor cells, however the overall effect of the presence of stromal components on Ce6 accumulation is negative (Ce6 accumulation in heterospheroids is lower than that in homospheroids).…”

Section: Discussionmentioning

confidence: 99%

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

Yakavets

Samuel

François

et al. 2019

JCM

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Conventional 3D multicellular tumor spheroids of head and neck squamous cell carcinoma (HNSCC) consisting exclusively of cancer cells have some limitations. They are compact cell aggregates that do not interact with their extracellular milieu, thus suffering from both insufficient extracellular matrix (ECM) deposition and absence of different types of stromal cells. In order to better mimic in vivo HNSCC tumor microenvironment, we have constructed a 3D stroma-rich in vitro model of HNSCC, using cancer-associated MeWo skin fibroblasts and FaDu pharynx squamous cell carcinoma. The expression of stromal components in heterospheroids was confirmed by immunochemical staining. The generated co-culture FaDu/MeWo spheroids were applied to study penetration, distribution and antitumor efficacy of photoactive drugs such as Temoporfin and Chlorin e6 used in the photodynamic therapy flow cytometry and fluorescence microscopy techniques. We also investigated the distribution of photodiagnostic agent Indocyanine Green. We demonstrated that the presence of stroma influences the behavior of photoactive drugs in different ways: (i) No effect on Indocyanine Green distribution; (ii) lower accumulation of Chlorin e6; (iii) better penetration and PDT efficiency of Temoporfin. Overall, the developed stroma-rich spheroids enlarge the arsenal of in vitro pre-clinical models for high-throughput screening of anti-cancer drugs.

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“…The aggregation leads to the loss of a photodynamic efficacy [16]. To prevent the aggregation process, the PS can be loaded into the polymer water-soluble nanoplatform [17,18]. It is known that the ideal drug delivery system can be switched-on by responding to biological stimuli.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Dextran-Poly(N-Isopropylacrylamide) Copolymer as a Potential Temperature-Dependent Nanocarrier for Photosensitizers with Different Properties

et al. 2020

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Thermosensitive polymer poly-N-isopropylacrylamide (PNIPAM) having a conformational transition in the interval of physiological temperatures was discussed last years as a novel drug delivery system. Chlorin e6 (Ce6) is a photosensitizer used in the photodynamic anticancer therapy. The comparative study of the encapsulation of Ce6 and its derivative, dimethylether of chlorine e6 (DME Ce6), into a water-soluble star-like PNIPAM-based copolymer to prevent the aggregation of a photosensitizer in the water medium is carried out. The photophysical properties of the copolymer/photosensitizer complexes as functions of the temperature in the region of the conformational transition of the polymer matrix have been studied and discussed. It is shown that Ce6 at low temperatures interacts weakly with the polymer phase. As a result, the absorption and fluorescence properties of Ce6 in aqueous and polymer solutions are practically identical. Fluorescence characteristics of Ce6 in a copolymer solution remain unchanged, when it is heated, which indicates the lack of a possibility for this sensitizer to bind in the bulk of the polymer phase. Following fluorescence data, all DME Ce6 molecules are bound with the polymer matrix, when a temperature is higher than the Lower Critical Solution Temperature (LCST) of the polymer. The formed complexes are quite stable. In the presence of serum proteins, the molecules of the photosensitizer remain associated for a long time with the polymer. At temperatures below LCST, DME Ce6 is not bound by the polymer. Moreover, the cooling of a solution of DME Ce6/polymer complexes leads to the rapid dissociation of photosensitizer molecules with subsequent aggregation or binding to biological structures in an aqueous medium. The obtained results show that the possibility of using the polymer PNIPAM as a temperature-dependent nanocarrier strongly depends on the properties of the loaded drug.

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Polylactide-Based Block Copolymeric Micelles Loaded with Chlorin e6 for Photodynamic Therapy: In Vitro Evaluation in Monolayer and 3D Spheroid Models

Cited by 29 publications

References 52 publications

Rational Design of IR820‐ and Ce6‐Based Versatile Micelle for Single NIR Laser–Induced Imaging and Dual‐Modal Phototherapy

Rational Design of IR820‐ and Ce6‐Based Versatile Micelle for Single NIR Laser–Induced Imaging and Dual‐Modal Phototherapy

Stroma-Rich Co-Culture Multicellular Tumor Spheroids as a Tool for Photoactive Drugs Screening

Evaluation of a Dextran-Poly(N-Isopropylacrylamide) Copolymer as a Potential Temperature-Dependent Nanocarrier for Photosensitizers with Different Properties

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