Dual-Modal Imaging-Guided Theranostic Nanocarriers Based on Indocyanine Green and mTOR Inhibitor Rapamycin

Abstract

The development of treatment protocols that resulted in a complete response to photothermal therapy (PTT) was usually hampered by uneven heat distribution and low effectiveness. Here, we reported an NIR fluorescence and photoacoustic dual-modal imaging-guided active targeted thermal sensitive liposomes (TSLs) based on the photothermal therapy agent Indocyanine green (ICG) and antiangiogenesis agent Rapamycin (RAPA) to realize enhanced therapeutic and diagnostic functions. As expected, the in vitro drug release studies exhibited the satisfactory result of drug released from the TSLs under hyperthermia conditions induced by NIR stimulation. The in vitro cellular studies confirmed that the FA-ICG/RAPA-TSLs plus NIR laser exhibited efficient drug accumulation and cytotoxicity in tumor cells and epithelial cells. After 24 h intravenous injection of FA-ICG/RAPA-TSLs, the margins of tumor and normal tissue were accurately identified via the in vivo NIR fluorescence and photoacoustic dual-modal imaging. In addition, FA-ICG/RAPA-TSLs combined with NIR irradiation treated tumor-bearing nude mice inhibited tumor growth to a great extent and possessed much lower side effects to normal organs. All detailed evidence suggested that the theranostic TSLs which were capable of enhancing the therapeutic index might be a suitable drug delivery system for dual-modal imaging-guided therapeutic tools for diagnostics as well as the treatment of tumors.

Cyanine based Nanoprobes for Cancer Theranostics

“…To maximize therapeutic efficiency, fluorescent and PA imaging property of NIR dyes are often implemented to predict biodistribution and accumulation of NPs followed by subsequently targeted phototherapy in selected tumor region . Recently, a PA and NIRF imaging‐guided active targeted TSLs co‐encapsulating ICG and Rapamycin showed enhanced therapeutic and diagnostic function . Strong fluorescence and PA signal acquired from folate‐targeted ICG/RAPA liposomes agreed well to demonstrate excellent tumor targeting capability of the probe at 24 h post injection.…”

“…b) Illustration of the Theranostic TSLs: (a) Structure of FA‐ICG/RAPA‐TSLs and (b) Antitumor mechanism of FAICG/RAPA‐TSLs. Reproduced with permission . Copyright 2016, American Chemical Society.…”

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

“…However, numerous disadvantages, including poor solubility in aqueous media and low photostability, generally limit biomedical applications. 16 The applicability of insoluble RSV is also limited by its poor stability in aqueous solutions. 29 Figure 4A and B shows the fluorescence stability of ICG and FARIPNPs in aqueous solution at 4°C and 37°C, respectively.…”

“…[9][10][11][12] Nevertheless, effective and prolonged tumor imaging applications of ICG are restricted by a tendency of the compound to aggregate and degrade in aqueous solutions with concentration dependence, poor photostability, lack of target specificity and quick body clearance (t 1/2 =2−4 min). [13][14][15][16] To overcome these drawbacks, various nanoparticle formulations of ICG, such as encapsulation approaches using polymer and liposomes, as well as physical adsorption with 2-dimensional materials, including graphene and derivatives, transition metal dichalcogenides and so on, have been reported. [16][17][18][19] However, noncovalent interactions tend to be weak in nature, often resulting in premature release of the compound from the carriers, which may influence the imaging applicability of the nanoprobes.…”

“…[13][14][15][16] To overcome these drawbacks, various nanoparticle formulations of ICG, such as encapsulation approaches using polymer and liposomes, as well as physical adsorption with 2-dimensional materials, including graphene and derivatives, transition metal dichalcogenides and so on, have been reported. [16][17][18][19] However, noncovalent interactions tend to be weak in nature, often resulting in premature release of the compound from the carriers, which may influence the imaging applicability of the nanoprobes. 20 Therefore, covalent conjugation of ICG with nanomaterials may feature a more rational strategy for ICG delivery.…”