Stability Of Indocyanine Green Research Articles

Development of Indocyanine Green/Methyl-β-cyclodextrin Complex-Loaded Liposomes for Enhanced Photothermal Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-β-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

In vitro Function Study of Different Negative Charge Pullulan Nanoparticles for Sentinel Lymph Node Angiography.

Many dyes or radioactive markers used for sentinel lymph node (SLN) have the shortcomings of false positive and radiation injury. Indocyanine green (ICG) seems to have a lower false positive rate and tissue damage, without a clear field of vision during the operation. For the shortcomings, we successfully synthesized three anionic pullulan materials, changed the degree of hydrophobic for size controlling (< 50nm) to prepare CHP nanoparticles (NPs) and changed the succinyl degree to prepare CHPC NPs with different negative surface potential. The size of those NPs were less than 50nm under (transmission electron microscope) TEM, with hydrodynamic size of 90.67 ± 2.2 nm of CHP, 105.8 ± 1.7 nm of CHPC1 and 115.9 ± 2.3 nm of CHPC2. Moreover, the Zeta potential of CHP, CHPC1 and CHPC2 were -1.9 ± 0.2 mV, -9.6 ± 0.3 mV and -19.4 ± 0.7 mV. The size of ICG-loading CHP, CHPC1 and CHPC2 NPs increased to 109.4 ± 2.7 nm, 113.8 ± 1.2 nm and 30.6 ± 3.5 nm, as the zeta potential decreased to -2.7 ± 0.4 mV, -12.5 ± 1.6 mV and -23.1 ± 1.2 mV. With the increasing degree of succinyl, the size increased and the zeta potential decreased. At the same time, the higher degree of succinyl drug-loading NPs have lower release and have increased the stability of ICG. We found that the blank-NPs had no significant toxicity to normal cells (HSF), as the ICG@CHP group had larger toxicity than the CHPCs and control. Moreover, the cellular uptake was decreased with the increased degree of succinyl. In this study, we successfully prepared CHPC2 carriers with the maximum negative surface charge, for follow-up research and providing new ideas for SLN.

Contrast-Enhanced Multispectral Optoacoustic Tomography for Functional Assessment of the Gastrointestinal Tract.

Real-time imaging and functional assessment of the intestinal tract and its transit pose a significant challenge to conventional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular-sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in deep tissue. Herein, a novel approach using the orally administered clinical-approved fluorescent dye indocyanine green (ICG) for bedside, non-ionizing evaluation of gastrointestinal passage is presented. The authors are able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple time points over eight hours after ingestion of a standardized meal with and without ICG. ICG signals can be visualized and quantified in different intestinal segments, while its excretion is confirmed by fluorescent imaging of stool samples. These findings indicate that contrast-enhanced MSOT (CE-MSOT) provides a translatable real-time imaging approach for functional assessment of the gastrointestinal tract.

Abstract 817: Effective near infrared laser-induced photothermal therapy for cancer using indocyanine green/methyl-Β-cyclodextrin compound loaded liposomal nanoparticle

Abstract Background: Photothermal therapy (PTT) is a promising cancer therapeutic process to eliminate solid cancer through thermal ablation using electromagnetic radiation and photothermal agent (PTA). PTT is efficient in treating tumor because tumor has a lower heat resistance due to the shortage of blood supply. Also, it has less invasiveness, low toxicity to normal tissues, high spatial specificity, and minimal drug resistance. Indocyanine green (ICG), an FDA approved agent, is a widely used as a PTA and imaging probe in clinical application. However, ICG has several major shortcomings that may hinder its practical use such as short half-life in circulatory system, unspecific binding to protein, and rapid decomposition by heat, light and aqueous solution, resulting in a decrease in PTT efficacy. To overcome these problems, we developed ICG/methyl-beta-cyclodextrin (MB-CD) compound-loaded liposomal nanoparticle by host-guest complexation between ICG and MB-CD and its liposome formation. It was possible to improve ICG stability and anti-tumor efficacy. Method: Liposomes were synthesized using 1,2-Distearoyl-sn-glycero-3-phosphoethanolamone-N-(methoxy-(polyethylene glycol)-5000), 1,2-Distearoyl-sn-glycero-3-phosphocholine, cholesterol, methanol, and chloroform by film hydration method. To form ICG/MB-CD compound (IDC), ICG and MB-CD solution were mixed and purified. Then it was loaded into liposomal nanoparticles and filtered to prepare ICG/MB-CD compound-loaded liposome (IDL). Results: We compared ICG, IDC, indocyanine green loaded liposome (ICL), and IDL. IDC and IDL were characterized by absorbance spectra, fluorescence spectrometer, dynamic light scattering, and transmission electron microscopy. IDL was less decomposed in various solvents than others, indicating of higher in vitro stability. Moreover, IDL had an enhanced fluorescence intensity among the four groups due to the protection of ICG conjugated structure by MB-CD. In addition, it was remarkable for IDL to be the least bleached by near infrared laser compared to others for demonstrating its better photothermal stability and retention ability. In confocal imaging and in vitro PTT experiment using 4T1 breast cancer cell line, IDL was well uptaken by the cells and showed the highest cancer therapeutic efficacy. Furthermore, in vivo and ex vivo fluorescence imaging were performed using 4T1 tumor bearing mice after intravenous injection of the particles. As a result, IDL injected group demonstrated the highest tumor uptake among the four groups. Conclusions: IDL was successfully synthesized and exhibited excellent optical property, stability, and anti-tumor efficacy. Thus, it could be a promising PTA for treatment of solid cancer. Citation Format: MinKyu Kim, Hyung-Jun Im. Effective near infrared laser-induced photothermal therapy for cancer using indocyanine green/methyl-Β-cyclodextrin compound loaded liposomal nanoparticle [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 817.

Design development and optimisation of multifunctional Doxorubicin-loaded Indocynanine Green proniosomal gel derived niosomes for tumour management

This study presents the design, development, and optimization of multifunctional Doxorubicin (Dox)-loaded Indocyanine Green (ICG) proniosomal gel-derived niosomes, using Design of Experiments (23 factorial model). Herein, the multifunctional proniosomal gel was prepared using the coacervation phase separation technique, which on hydration forms niosomes. The effect of formulation variables on various responses including Zeta potential, Vesicle size, entrapment efficiency of Dox, entrapment efficiency of ICG, Invitro drug release at 72nd hour, and NIR hyperthermia temperature were studied using statistical models. On the basis of the high desirability factor, optimized formulation variables were identified and validated with the experimental results. Further, the chemical nature, vesicle morphology, surface charge, and vesicle size of optimized proniosomal gel-derived niosomes were evaluated. In addition, the effect of free ICG and bound ICG on NIR hyperthermia efficiency has been investigated to demonstrate the heating rate and stability of ICG in the aqueous environment and increased temperature conditions. The drug release and kinetic studies revealed a controlled biphasic release profile with complex mechanisms of drug transport for optimized proniosomal gel-derived niosomes. The potential cytotoxic effect of the optimised formulation was also demonstrated invitro using HeLa cell lines.

Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process

Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.

Polyethylene glycol-modified mesoporous polydopamine nanoparticles co-loaded with dimethylcurcumin and indocyanine green for combination therapy of castration-resistant prostate cancer

Herein, polyethylene glycol-modified mesoporous polydopamine (PEG-MPDA) nanoparticles co-loaded with indocyanine green (ICG) and dimethylcurcumin (ASC-J9, DMC) were developed for combination therapy of castration-resistant prostate cancer. MPDA nanoparticles were prepared and surface modified with methoxypolyethylene glycol amine (mPEG-NH2, M.W. 2000 and 5000). The prepared PEG2000-MPDA and PEG5000-MPDA nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). ICG and DMC co-loaded PEG2000-MPDA and PEG5000-MPDA nanoparticles (PEG2000-MPDA@ICG&DMC and PEG5000-MPDA@ICG&DMC) were prepared by a solvent diffusion method. The decrease in drug feeding ratios results in decline in drug loading content and increase in drug encapsulation rate. PEG2000-MPDA@ICG&DMC and PEG5000-MPDA@ICG&DMC nanoparticles with relatively high drug loading content (ICG 10.0 ± 0.5% and 9.2 ± 0.3%, DMC 6.7 ± 0.2% and 6.4 ± 0.3%) were selected for further studies. The hydrodynamic diameters of these two nanoparticles are between 200 and 300 nm. These two nanoparticles display enhanced stability of ICG in aqueous solution, near-infrared (NIR) laser irradiation-promoted DMC release, efficient photothermal effect, enhanced cellular uptake, and excellent biocompatibility. In in vitro antitumor effect study, these two nanoparticles exhibit enhanced antitumor effect against 22Rv1 cells as compared to ICG&DMC mixture upon 808 nm laser irradiation. Western blot analyses indicate that these two nanoparticles enhance the degradation of androgen receptor (AR) significantly. This work provides a novel strategy and an effective co-delivery system for combinational castration-resistant prostate cancer therapy.

Liposome-based multifunctional nanoplatform as effective therapeutics for the treatment of retinoblastoma

Photothermal therapy has the characteristics of minimal invasiveness, controllability, high efficiency, and strong specificity, which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. However, due to the limited tissue penetration of infrared light, it is difficult to promote and apply in clinical practice. The eye is the only transparent tissue in human, and infrared light can easily penetrate the eye tissue, so it is expected that photothermal therapy can be used to treat fundus diseases. Here in, a new nano-platform assembled by liposome and indocyanine green (ICG) was used to treat retinoblastoma. ICG was assembled in liposomes to overcome some problems of ICG itself. For example, ICG is easily quenched, self-aggregating and instability. Moreover, liposomes can prevent free ICG from being cleared through the systemic circulation. The construction of the nano-platform not only ensured the stability of ICG in vivo, but also realized imaging-guide photothermal therapy, which created a new strategy for the treatment of retinoblastoma.

RGD-targeted redox responsive nano micelle: co-loading docetaxel and indocyanine green to treat the tumor

Cancer, also known as a malignant tumor, has developed into a type of disease with the highest fatality rate, seriously threatening the lives and health of people. Chemotherapy is one of the most important methods for the treatment of cancer. However, chemotherapy drugs have some problems, such as low solubility and lack of targeting, which severely limit their clinical applications. To solve these problems, we designed a block copolymer that has a disulfide bond response. The polymer uses RGD peptide (arginine-glycine-aspartic acid) as the active targeting group, PEG (polyethylene glycol) as the hydrophilic end, and PCL (polycaprolactone) as the hydrophobic end. Then we utilized the amphiphilic polymer as a carrier to simultaneously deliver DOC (docetaxel) and ICG (indocyanine green), to realize the combined application of chemotherapy and photothermal therapy. The antitumor efficacy in vivo and histology analysis showed that the DOC/ICG-loaded micelle exhibited higher antitumor activity. The drug delivery system improved the solubility of DOC and the stability of ICG, realized NIR-guided photothermal therapy, and achieved an ideal therapeutic effect.

Indocyanine Green Loaded Modified Mesoporous Silica Nanoparticles as an Effective Photothermal Nanoplatform.

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO2-NH2 NPs). SiO2-NH2 NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO2 NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO2 NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO2-NH2 NPs by electrostatic attraction to enable SiO2-NH2@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO2-NH2 was greatly increased compared to unmodified SiO2, and the stability of ICG was also improved. Moreover, the SiO2-NH2@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO2-NH2@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells.

ICG-Loaded PEGylated BSA-Silver Nanoparticles for Effective Photothermal Cancer Therapy.

PurposeIndocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy.Methods and ResultsPEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG (“PEG-BSA-AgNP/ICG”). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity.ConclusionOur findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.

Non-ionic polysorbate-based nanoparticles for efficient combination chemo/photothermal/photodynamic therapy

Combination therapy has gained great attraction as an effective strategy for the treatment of cancers. In this study, non-ionic polysorbate-based nanoparticles were prepared for combination chemo/photothermal/photodynamic cancer therapy via effective intracellular delivery of piperlongumine (PL) and indocyanine green (ICG). PL was used as a pro-oxidant drug that can induce selective apoptosis through the increase of oxidative stress in cancer cells. ICG was used as a near-infrared (NIR) light-absorbing photothermal and photodynamic agent. Non-ionic Tween 80 (T80) polysorbate was used to prepare PL- and ICG-loaded micelles with nanoscale diameters. Both PL and ICG were efficiently encapsulated in the T80-based micelles. Storage stability of ICG in aqueous solutions was greatly improved by encapsulation into the T80-based micelles. ICG-loaded T80 micelles (ICG-T80) showed higher photothermal conversion efficiency than free ICG. T80 also increased cellular uptake of ICG. Moreover, ICG-T80 showed NIR light-triggered reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells, owing to the photodynamic effects of NIR light-absorbing ICG. PL-loaded T80 micelles also increased intracellular ROS levels in MCF-7 cells owing to the pro-oxidant activity of PL. In vitro study showed that ICG-T80 micelles exhibited efficient anticancer activity under NIR irradiation via combined photothermal therapy (PTT) and photodynamic therapy (PDT). PL- and ICG-loaded T80 micelles (PL-ICG-T80) further increased the cytotoxicity via combined chemo/PTT/PDT. PL-ICG-T80 also showed cancer-selective cytotoxicity. This study demonstrates that PL-ICG-T80 micelles are effective for NIR light-triggered combination chemo/PTT/PDT.

Engineering of an intelligent cascade nanoreactor for sequential improvement of microenvironment and enhanced tumor phototherapy

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a new tumor treatment method with high specificity, low toxicity and non-invasive advantages. Herein, we synthesized hyaluronic acid (HA) modified mesoporous Prussian blue (PB) nanoparticles (HA-PB NPs) with macrophage transformation (pro-tumor M2 to anti-tumor M1) and self-produced oxygen (O2) properties. After that, the photosensitizer indocyanine green (ICG) was loaded, to realize PTT and PDT synergistic treatment of 4T1 tumor under a single near-infrared (NIR) laser irradiation. In vitro experiments showed that HA-PB can improve the stability of ICG. Drug release experiment proved the acidic tumor microenvironment containing rich hyaluronidase (HAase) could achieve local and specific drug release in targeted tumor tissue. HA-PB can be internalized by 4T1 cells and M2 macrophages. After M2 phenotype being reversed into M1 macrophages, H2O2 secreted by M1 can be catalyzed by HA-PB nanozyme to generate O2 for tumor microenvironment improvement and O2 self-supplied PDT. With co-culture of M2 macrophages and 4T1 cells, HA-PB/ICG could effectively induce DNA breakage (37.9 ± 3.2%) and tumor cell apoptosis. In vivo results indicated that HA-PB/ICG can enhance the accumulation capacity and retention time of ICG at the tumor site. Under 808 nm laser irradiation, the temperature and ROS level of tumor site in HA-PB/ICG group raised 22.7 °C and 32 folds, respectively, showing superior photothermal and ROS conversion abilities. Furthermore, pharmacodynamic results proved that HA-PB/ICG nanoplatform can significantly inhibit 4T1 tumor proliferation with V/V0 of 0.31 ± 0.16, by precise and synchronous PTT and O2 self-supplied PDT.

NIR light-induced tumor phototherapy using ICG delivery system based on platelet-membrane-camouflaged hollow bismuth selenide nanoparticles

Near-infrared (NIR) light-triggered photothermal therapy (PTT) is a promising treatment strategy for treating cancer. The combination of nanotechnology and NIR has been widely applied. However, the therapeutic efficacy of the drug-delivery system depends on their ability to avoid phagocytosis of endothelial system, cross the biological barriers, prolong circulation life, localize and rapidly release the therapeutic at target sites. In this work, we designed a platelet membrane (PM)-camouflaged hollow mesoporous bismuth selenide nanoparticles (BS NPs) loading with indocyanine green (ICG) (PM@BS-ICG NPs) to achieve the above advantages. PM-coating has active tumor-targeting ability which could prevent drug leakage and provide drug long circulation, causing drug delivery systems to accumulate in tumor sites effectively. Moreover, as a type of the photothermal sensitizers, BS NPs are used as the inner cores to improve ICG stability and are served as scaffolds to enhance the hardness of this drug delivery system. For one hand, the thermal vibration of BS NPs under NIR laser irradiation causes tumor inhibition through hyperthermia. For another hand, this hyperthermia process could damage PM and let ICG rapid release from PM@BS-ICG NPs. The in vitro and in vivo results showed that this biomimetic nano-drug delivery system exhibits obvious antitumor activity which has good application prospect.

Indocyanine green loaded APTMS coated SPIONs for dual phototherapy of cancer

Superparamagnetic iron oxide nanoparticles (SPIONs) have been recently recognized as highly efficient photothermal therapy (PTT) agents. Here, we demonstrate, for the first time to our knowledge, dose and laser intensity dependent PTT potential of small, spherical, 3-aminopropyltrimethoxysilane coated cationic superparamagnetic iron oxide nanoparticles (APTMS@SPIONs) in aqueous solutions upon irradiation at 795 nm. Indocyanine green (ICG) which has been recently used for photodynamic therapy (PDT), was loaded to APTMS@SPIONs to improve the stability of ICG and to achieve an effective mild PTT and PDT (dual therapy) combination for synergistic therapeutic effect on cancer cells via a single laser treatment in the near infrared (NIR). Neither APTMS@SPIONs nor ICG-APTMS@SPIONs showed dark toxicity on MCF7 breast and HT29 colon cancer cell lines. A safe laser procedure was determined as 10 min irradiation at 795 nm with 1.8 W/cm2 of laser intensity, at which APTMS@SPION did not cause a significant cell death. However, free ICG reduced cell viability at and above 10 μg/ml under these conditions along with generation of reactive oxygen species (ROS), more effectively in MCF7. ICG-APTMS@SPION treated cells showed 2-fold increase in ROS generation and near complete cell death at and below 5 μg/ml ICG dose, even in less sensitive HT29 cells after a single laser treatment at NIR, which would be safe for the healthy tissue and provide a longer penetration depth. Besides, both components can be utilized for diagnosis and the overall composition may be used for optical-image guided phototherapy in the NIR region.

Pea Protein/Gold Nanocluster/Indocyanine Green Ternary Hybrid for Near-Infrared Fluorescence/Computed Tomography Dual-Modal Imaging and Synergistic Photodynamic/Photothermal Therapy.

Developments in technology such as theranostic nanoplatforms, which combine complementary imaging modalities and synergistic therapies, have brought new hope to the diagnosis and treatment of cancer, one of the most deadly diseases. In this article, a nanoplatform (AuNCs/PPI-ICG nanohybrid) with a theranostic effect was prepared using indocyanine green (ICG), a cyanine dye with bright near-infrared fluorescence (NIRF) and excellent photodynamic and photothermal performance, and it was loaded onto gold nanoclusters/pea protein isolate hybrid nanoparticles (AuNCs/PPI NPs). There was a linear relationship between ICG loading ratio and the concentration, within a concentration range of 0-5 mg/mL, making it possible to precisely control the concentration of loaded ICG. In addition, the AuNCs/PPI-ICG nanohybrid displayed outstanding loading stability and enhanced the aqueous stability of ICG, owing to the protectivity of AuNCs/PPI NPs. In vitro cell experiments showed that this biocompatible nanohybrid could be taken up by A549 cells and used as a fluorescent bioimaging probe. Moreover, because of Au, AuNCs/PPI NPs could also act as a potential computed tomographic (CT) contrast agent, and so the AuNCs/PPI-ICG nanohybrid had the potential to function as a dual-modal imaging agent. Finally, the as-prepared hybrid, with excellent photodynamic properties and exceptional photothermal capabilities, showed a satisfactory therapeutic effect in ablating A549 cancer cells. These results convincingly demonstrate that the AuNCs/PPI-ICG nanohybrid is a promising theranostic nanoplatform for NIRF/CT dual-modal imaging and for synergistic photodynamic therapy/photothermal therapy (PDT/PTT).

Reactive oxygen species and near-infrared light dual-responsive indocyanine green-loaded nanohybrids for overcoming tumour multidrug resistance

The nucleus is in charge of the metabolism and heredity of the cell, and genetic mutations are closely related with tumour multidrug resistance (MDR). Indocyanine green (ICG), the FDA-approved photosensitizer, is widely used for tumour photodynamic therapy (PDT) and photothermal therapy (PTT). Few studies have clarified the cellular distribution of ICG in MDR tumour cells. In the study, ICG distribution was detected in the whole tumour cells of MCF-7 and MCF-7/ADR, especially in the nucleus, which led us to question whether increasing cellular accumulation and nuclear distribution of ICG could be a potential method to overcome MDR. Therefore, a reactive oxygen species (ROS) and near-infrared (NIR) light dual-responsive nanohybrid was constructed with diselenide cross-linked polyamidoamine-Poloxamer 188 and graphene oxide with ICG as payloads (ICG/GPP). The nanohybrid enhanced the stability of ICG and showed an ROS-sensitive release behaviour. More ICG was delivered by ICG/GPP to the MCF-7/ADR cells. After escaping from the lysosome, nuclear accumulation of ICG was increased. Under NIR laser irradiation, ICG/GPP showed increased cytotoxicity for the combined PTT and PDT in MCF-7/ADR cells. Moreover, the expression of P-glycoprotein (P-gp) was suppressed to overcome tumour MDR. The ROS- and NIR- responsive GPP shows potential for the nuclear delivery of drugs to combat tumour MDR.

Development of Rifampicin-Indocyanine Green-Loaded Perfluorocarbon Nanodroplets for Photo-Chemo-Probiotic Antimicrobial Therapy.

Acne vulgaris, generally resulted from overgrowth of Propionibacterium acnes (P. acnes), is one of the most difficult-to-treat facial dermatoses and more than 90% of adolescents experienced the disease worldwide. Because the innate non-lymphoid immune system cannot effectively eliminate excessive P. acnes from the skin surface, so far the therapy of acne vulgaris is still mainly dependent on antibiotic treatment. However, long-term or overdose of antibiotics may initiate microbial drug resistance and/or generate unexpected side effects that seriously hamper the use of antibiotics in the clinic. To overcome the aforementioned challenges, the novel rifampicin (RIF)-indocyanine green (ICG)-loaded perfluorocarbon (PFC) nanodroplets (RIPNDs) that may offer combined photo-, chemo-, and probiotic efficacies to P. acnes eradication were developed in this study. The RIPND was first characterized as a sphere-like nanoparticle with surface charge of −20.9 ± 2.40 mV and size of 240.7 ± 6.73 nm, in which the encapsulation efficiencies of RIF and ICG were 54.0 ± 10.5% and 95.0 ± 4.84%, respectively. In comparison to the freely dissolved ICG, the RIPNDs conferred an enhanced thermal stability to the entrapped ICG, and were able to provide a comparable hyperthermia effect and markedly increased production of singlet oxygen under near infrared (NIR; 808 nm, 6 W/cm2) exposure. Furthermore, the RIPNDs were able to induce fermentation of S. epidermidis but not P. acnes, indicating that the RIPNDs may serve as a selective fermentation initiator for the target probiotics. Based on the microbial population index analyses, P. acnes with 1 × 106 cells/mL can be completely eradicated by 12-h co-culture with S. epidermidis fermentation products followed by treatment of RIPNDs (≥20-μM ICG/3.8-μM RIF) + NIR for 5 min, whereby the resulted microbial mortality was even higher than that caused by using 16-fold enhanced amount of loaded RIF alone. Overall these efforts show that the RIPNDs were able to provide improved ICG stability, selective fermentability to S. epidermidis, and enhanced antimicrobial efficacy compared to equal dosage of free RIF and/or ICG, indicating that the developed nanodroplets are highly potential for use in the clinical anti-P. acne treatment with reduced chemotoxicity.

Preparation of photothermal palmitic acid/cholesterol liposomes.

Indocyanine green (ICG) is the only FDA-approved near-infrared dye and it is currently used clinically for diagnostic applications. However, there is significant interest in using ICG for triggered drug delivery applications and heat ablation therapy. Unfortunately, free ICG has a short half-life in vivo and is rapidly cleared from circulation. Liposomes have been frequently used to improve ICG's stability and overall time of effectiveness in vivo, but they have limited stability due to the susceptibility of phospholipids to hydrolysis and oxidation. In this study, nonphospholipid liposomes were used to encapsulate ICG, and the resulting liposomes were characterized for size, encapsulation efficiency, stability, and photothermal response. Using the thin-film hydration method, an ICG encapsulation efficiency of 54% was achieved, and the liposomes were stable for up to 12 weeks, with detectable levels of encapsulated ICG up to week 4. Additionally, ICG-loaded liposomes were capable of rapidly producing a significant photothermal response upon exposure to near-infrared light, and this photothermal response was able to induce changes in the mechanical properties of thermally responsive hydrogels. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1384-1392, 2019.

Anti-EGFR Indocyanine Green-Mitomycin C-Loaded Perfluorocarbon Double Nanoemulsion: A Novel Nanostructure for Targeted Photochemotherapy of Bladder Cancer Cells.

The use of phototherapy as an adjuvant bladder cancer treatment has long been considered, but its application has been severely hampered due to a lack of tumor specificity, unpredicted cytotoxicity, and insufficient anticancer efficacy. In this study, we aim to manufacture anti-EGFR indocyanine green (ICG) mitomycin C (MMC) encapsulated perfluorocarbon double nanoemulsions (EIMPDNEs), and explore their photochemotherapeutic efficacy on EGFR-expressing bladder cancer cells in vitro. The EIMPDNEs were manufactured using a double emulsification technique followed by antibody conjugation on the particles’ surfaces. The EIMPDNE were 257 ± 19.4 nm in size, with a surface charge of −12.3 ± 2.33 mV. The EGFR targetability of the EIMPNDE was confirmed by its enhanced binding efficiency to T24 cells when compared with the performance of nanodroplets without EGFR conjugation (p < 0.05). In comparison with freely dissolved ICG, the EIMPDNEs with equal ICG content conferred an improved thermal stability to the encapsulated ICG, and were able to provide a comparable hyperthermia effect and significantly enhanced the production of singlet oxygen under 808 nm near infrared (NIR) exposure with an intensity of 6 W cm−2 for 5 min (p < 0.05). Based on viability analyses, our data showed that the EIMPDNEs were effective in bladder cancer cell eradication upon NIR exposure (808 nm; 6 W cm−2), and the resulting cell death rate was even higher than that caused by a five-fold higher amount of entrapped MMC alone. With the merits of improved ICG stability, EGFR binding specificity, and effective cancer cell eradication, the EIMPDNEs exhibit potential for use in EGFR-expressing bladder cancer therapy with lower chemotoxicity.