Enhanced EPR directed and Imaging guided Photothermal Therapy using Vitamin E Modified Toco-Photoxil

Abstract

Herein we report synthesis, characterization and preclinical applications of a novel hybrid nanomaterial Toco-Photoxil developed using vitamin E modified gold coated poly (lactic-co-glycolic acid) nanoshells incorporating Pgp inhibitor d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a highly inert and disintegrable photothermal therapy (PTT) agent. Toco-Photoxil is highly biocompatible, physiologically stable PTT material with an average diameter of 130 nm that shows good passive accumulation (2.3% ID) in solid tumors when delivered systemically. In comparison to its surface modified counterparts such as IR780-Toco-Photoxil, FA-Toco-Photoxil or FA-IR780-Toco-Photoxil accumulation are merely ~0.3% ID, ~0.025% ID and ~0.005% ID in folate receptor (FR) negative and positive tumor model. Further, Toco-Photoxil variants are prepared by tuning the material absorbance either at 750 nm (narrow) or 915 nm (broad) to study optimal therapeutic efficacy in terms of peak broadness and nanomaterial’s concentration. Our findings suggest that Toco-Photoxil tuned at 750 nm absorbance is more efficient (P = 0.0097) in preclinical setting. Toco-Photoxil shows complete passiveness in critical biocompatibility test and reasonable body clearance. High tumor specific accumulation from systemic circulation, strong photothermal conversion and a very safe material property in body physiology makes Toco-Photoxil a superior and powerful PTT agent, which may pave its way for fast track clinical trial in future.

<p>Plasmonic MXene-based nanocomposites exhibiting photothermal therapeutic effects with lower acute toxicity than pure MXene</p>

“…In this context, because of their unique optical properties, noble metals such as gold (Au) and silver (Ag) exhibit a well-known photo-physical phenomenon called localized surface plasmon resonance, which contributes to enhancing their intrinsic photo-absorption characteristics 33–36. For this reason, they can be functionalized as image-guided photothermal cancer therapy37,38 or PTT agents due to their propensity to generate hyperthermia in tumor cells when irradiated with a laser light 39–41. Akin to Au- and Ag-structured nanoparticles, Ti 3 C 2 T x (MXene) nanocomposites, having transition metal element (titanium), exhibit a strong NIR absorption as well as subsequent light-to-heat conversion property resulting in photon-induced hyperthermia.…”

Tumor‐Targeting Glycol Chitosan Nanoparticles for Cancer Heterogeneity

“…Chauhan et al also reported a hybrid PTT agent, Toco-Photoxil, which consisted of a Pgp inhibitor d-α-tocopheryl PEG 1000 succinate (TPGS), gold nanoparticle and GC-modified poly(lactic-coglycolic acid) (PLGA) for the PTT of tumors (Figure 24a). [153] The gold nanoparticle layer of Toco-Photoxil could be generated via co-ordinate bond formation between gold seeds and the amine group of GC, so that the absorption wavelength of Toco-Photoxil could be tuned for the desired NIR wavelength (750 and 915 nm) in PTT (Figure 24b). Folic-acid-modified Toco-Photoxil (FA-Toco-Photoxil), and IR 780 fluorescent dye-tagged Toco-Photoxils (IR 780-Toco-Photoxil and IR 780-FA-Toco-Photoxil) were prepared for the tumor targeting and in vivo NIRF imaging, respectively.…”

“…a–e) Reproduced under the terms of the CC‐BY Creative Commons Attribution 4.0 International license. [ 153 ] Copyright 2018, The Authors, published by Springer Nature.…”

Leveraging Immunotherapy with Nanomedicine

“…[52][53][54] ii) More recently, the use of an external trigger combined with NPs has been investigated. This trigger could be ultrasounds, [55][56][57] photothermal therapy, [57][58][59] photodynamic therapy, [57,60,61] or even radiation therapy. [62,63] Most often, the approach consists in targeting the tumor blood vessel using an v 3 peptide to disrupt the neovessels with the external trigger in order to improve the delivery of the drug in a second time ( Figure 1B).…”