Liposomal Indocyanine Green Research Articles

Targeted blood-brain barrier penetration and precise imaging of infiltrative glioblastoma margins using hybrid cell membrane-coated ICG liposomes

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.Graphical abstract

Neutrophil-targeted liposomal platform: A shift in novel approach for early detection and treatment of cancer metastasis

Tumor metastasis is responsible for 90 % of cancer-associated deaths, and its early detection may decrease the likelihood of mortality. Studies have demonstrated that metastasis results from the interaction between “seeds” (tumor cells) and “soil” (pre-metastatic niche, PMN). As the first and most abundant immune cells to be recruited to PMN, neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth, promoting angiogenesis, and shaping an immune-suppressive microenvironment. In this study, two distinct types of sialic acid (SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the l-selectin receptor. One of these liposomes, named ICG@SAL, was used to encapsulate indocyanine green (ICG) and was specifically designed for the early detection of cancer metastasis. The other liposome, referred to as ABE/Cur@SAL, co-loaded abemaciclib (ABE) and curcumin (Cur), with the intention of suppressing the progression of metastatic tumor. Fluorescence imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes (ICG@CL). This suggested that ICG@SAL could detect tumor metastasis at an early stage. The therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T (Treg) cell proliferation, enhance effector T cell activity and reduce tumorigenic factor release, implying that ABE/Cur@SAL could inhibit tumor metastasis. Overall, our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor metastasis. ICG@SAL could be employed for the early detection of tumor metastasis, while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified.

Photodisruption of the Inner Limiting Membrane: Exploring ICG Loaded Nanoparticles as Photosensitizers.

The inner limiting membrane (ILM) represents a major bottleneck hampering efficient drug delivery to the retina after intravitreal injection. To overcome this barrier, we intend to perforate the ILM by use of a light-based approach which relies on the creation of vapor nanobubbles (VNBs) when irradiating photosensitizers with high intensity laser pulses. Upon collapse of these VNBs, mechanical effects can disrupt biological structures. As a photosensitizer, we explore indocyanine green (ICG) loaded nanoparticles (NPs) specifically designed for our application. In light of this, ICG liposomes and PLGA ICG NPs were characterized in terms of physicochemical properties, ICG incorporation and VNB formation. ICG liposomes were found to encapsulate significantly higher amounts of ICG compared to PLGA ICG NPs which is reflected in their VNB creating capacity. Since only ICG liposomes were able to induce VNB generation, this class of NPs was further investigated on retinal explants. Here, application of ICG liposomes followed by laser treatment resulted in subtle disruption effects at the ILM where zones of fully ablated ILM were alternated by intact regions. As the interaction between the ICG liposomes and ILM might be insufficient, active targeting strategies or other NP designs might improve the concept to a further extent.

Experience with Photodynamic Therapy Using Indocyanine Green Liposomes for Refractory Cancer.

We reported the development of an effective cancer treatment using a multidisciplinary treatment, including photodynamic therapy (PDT) with indocyanine green (ICG) liposomes and a combination of Lentinula edodes mycelia (LEM) and hydrogen gas inhalation therapy. ICG liposomes were prepared by adding 5 mg of ICG to 50 mL liposomes. Later, 25 mL of ICG liposomes were diluted with 250 mL of 5% glucose solution and administered intravenously to the patient. We selected the multi-laser delivery system (MLDS), a laser irradiator for performing PDT. Further, the patients received a combination of LEM and hydrogen gas inhalation therapy throughout the treatment. We reported two cases of PDT therapy, one with middle intrathoracic esophagus carcinoma and the other with hypopharyngeal cancer. In the first case, the MLDS laser was directly attached to the endoscope and directed to the cancer area with wavelengths of 810 nm. After the treatment, a biopsy demonstrated no tumor recurrence. In the second case, the patient was treated with endovascular PDT using ICG liposomes and MLDS fiber optics. Later, tumor shrinkage was demonstrated after the first round and disappeared after six months. In conclusion, the present findings suggest that the effect of PDT using ICG liposomes with LEM and hydrogen gas may eradicate cancer without burdening patients by enhancing tumor immunity.

Dual-Wavelength Photoacoustic Computed Tomography with Piezoelectric Ring-Array Transducer for Imaging of Indocyanine Green Liposomes Aggregation in Tumors.

Recently, indocyanine green (ICG), as an FDA-approved dye, has been widely used for phototherapy. It is essential to obtain information on the migration and aggregation of ICG in deep tissues. However, existing fluorescence imaging platforms are not able to obtain the structural information of the tissues. Here, we prepared ICG liposomes (ICG-Lips) and built a dual-wavelength photoacoustic computed tomography (PACT) system with piezoelectric ring-array transducer to image the aggregation of ICG-Lips in tumors to guide phototherapy. Visible 780 nm light excited the photoacoustic (PA) effects of the ICG-Lips and near-infrared 1064 nm light provided the imaging of the surrounding tissues. The aggregation of ICG-Lips within the tumor and the surrounding tissues was visualized by PACT in real time. This work indicates that PACT with piezoelectric ring-array transducer has great potential in the real-time monitoring of in vivo drug distribution.

Cell-Membrane Biomimetic Indocyanine Green Liposomes for Phototheranostics of Echinococcosis.

Echinococcosis is an important zoonotic infectious disease that seriously affects human health. Conventional diagnosis of echinococcosis relies on the application of large-scale imaging equipment, which is difficult to promote in remote areas. Meanwhile, surgery and chemotherapy for echinococcosis can cause serious trauma and side effects. Thus, the development of simple and effective treatment strategies is of great significance for the diagnosis and treatment of echinococcosis. Herein, we designed a phototheranostic system utilizing neutrophil-membrane-camouflaged indocyanine green liposomes (Lipo-ICG) for active targeting the near-infrared fluorescence diagnosis and photothermal therapy of echinococcosis. The biomimetic Lipo-ICG exhibits a remarkable photo-to-heat converting performance and desirable active-targeting features by the inflammatory chemotaxis of the neutrophil membrane. In-vitro and in-vivo studies reveal that biomimetic Lipo-ICG with high biocompatibility can achieve in-vivo near-infrared fluorescence imaging and phototherapy of echinococcosis in mouse models. Our research is the first to apply bionanomaterials to the phototherapy of echinococcosis, which provides a new standard for the convenient and noninvasive detection and treatment of zoonotic diseases.

Indocyanine Green Performance Enhanced System for Potent Photothermal Treatment of Bacterial Infection.

The instability in solution and aggregation-induced self-quenching of indocyanine green (ICG) have weakened its fluorescence and photothermal properties, thus inhibiting its application in practice. In this study, the cationic and anionic liposomes containing ICG were prepared based on 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-glycerol (DPPG), respectively. Molecular dynamics (MD) simulations demonstrate that ICG molecules are better distributed in the membranes of cationic DOTAP-based liposomes, leading to a superior fluorescence and photothermal performance. The liposomal ICG also shows the physical and photothermal stability during irradiation and long-term storage. On this basis, the prepared DOTAP-based liposomal ICG was encapsulated in the self-healing hydrogel formed by guar gum through the borate/diol interaction. The proposed liposomal ICG-loaded hydrogel can not only convert near-infrared (NIR) light into heat effectively but also repair itself without external assistance, which will realize potent photothermal therapy (PTT) against bacterial infection and provide the possibility for meeting the rapidly growing needs of modern medicine.

Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy

BackgroundCancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice.ResultsHerein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration.ConclusionsOur research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system.Graphical

Vascular permeability in chronic rhinosinusitis enhances accumulation and retention of nanoscale pegylated liposomes

Chronic rhinosinusitis (CRS) is a debilitating inflammatory disorder of the sinonasal mucosa that substantially diminishes patient quality of life. Progress surrounding management of this disease has been crippled by a lack of therapeutic innovation. It has been posited that increased vascularity within the diseased sinuses of patients with CRS may allow for improved systemic drug delivery via nanoscale liposomal carriers. Such a system could enhance drug distribution, accumulation, and retention within the sinuses, ultimately leading to improved patient outcomes. PEGylated liposomes loaded with indocyanine green (ICG) were synthesized, characterized and systemically administered in a mouse model of CRS. Accumulation and retention of ICG in sinonasal tissue were evaluated. Compared to healthy controls, CRS mice showed significant sinonasal tissue accumulation and retention of PEGylated liposomal ICG for up to 21 days (P < 0.001). Conversely, free ICG was eliminated from the body after 24 h in both groups.

The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed destructive arthritis and enthesitis

BackgroundMcH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16–1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice.MethodsMale McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16–1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines.ResultsTissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16–1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16–1 treated groups.ConclusionsAdministration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.

Size and lipid modification determine liposomal Indocyanine green performance for tumor imaging in a model of rectal cancer

Localization of rectal tumors is a challenge in minimally invasive surgery due to the lack of tactile sensation. We had developed liposomal indocyanine green (Lip-ICG) for localization of rectal tumor. In this study we evaluated the effects of liposome size and lipid PEGylation on imaging. We used an endoscopically-guided orthotopic experimental rectal cancer model in which tumor fluorescence was determined at different time points after intravenous (i.v.) administration of Lip-ICG and PEGylated liposomes (PEG-Lip-ICG). Signal intensity was measured by tumor-to-background ratio (TBR), or normalized TBR (compared to TBR of free ICG). Fluorescence microscopy of tumor tissue was performed to determine fluorescence localization within the tissue and blood vessels. Liposomes of 60 nm showed an increased TBR compared with free ICG at 12 hours after i.v. injection: normalized TBR (nTBR) = 3.11 vs. 1, respectively (p = 0.006). Larger liposomes (100 nm and 140 nm) had comparable signal to free ICG (nTBR = 0.98 ± 0.02 and 0.78 ± 0.08, respectively), even when additional time points were examined (0.5, 3 and 24 hours). PEG-Lip- ICG were more efficient than Lip-ICG (TBR = 4.2 ± 0.18 vs. 2.5 ± 0.12, p < 0.01) presumably because of reduced uptake by the reticulo-endothelial system. ICG was found outside the capillaries in tumor margins. We conclude that size and lipid modification impact imaging intensity.

The effect of light sensitizer localization on the stability of indocyanine green liposomes

Light triggered drug delivery systems offer attractive possibilities for sophisticated therapy, providing both temporal and spatial control of drug release. We have developed light triggered liposomes with clinically approved indocyanine green (ICG) as the light sensitizing compound. Amphiphilic ICG can be localized in different compartments of the liposomes, but the effect of its presence, on both triggered release and long term stability, has not been studied. In this work, we report that ICG localization has a significant effect on the properties of the liposomes. Polyethylene glycol (PEG) coating of the liposomes leads to binding and stabilization of the ICG molecules on the surface of the lipid bilayer. This formulation showed both good storage stability in buffer solution (at +4–37 °C) and adequate stability in serum and vitreous (at +37 °C). The combination of ICG within the lipid bilayer and PEG coating lead to poor stability at elevated temperatures of +22 °C and + 37 °C. The mechanisms of the increased instability due to ICG insertion in the lipid bilayer was elucidated with molecular dynamics simulations. Significant PEG insertion into the bilayer was induced in the presence of ICG in the lipid bilayer. Finally, feasibility of freeze-drying as a long term storage method for the ICG liposomes was demonstrated. Overall, this is the first detailed study on the interactions of lipid bilayer, light sensitizer (ICG) and PEG coating on the liposome stability. The localization of the light triggering agent significantly alters the structure of the liposomes and it is important to consider these aspects in triggered drug delivery system design.

Synovitis in mice with inflammatory arthritis monitored with quantitative analysis of dynamic contrast-enhanced NIR fluorescence imaging using iRGD-targeted liposomes as fluorescence probes.

BackgroundRheumatoid arthritis (RA) is a common inflammatory disorder characterized primarily by synovitis and pannus formation in multiple joints, causing joints destruction and irreversible disability in most cases. Early diagnosis and effective therapy monitoring of RA are of importance for achieving the favorable prognosis.MethodsWe first prepared the targeted fluorescence probes, and then explored the feasibility of near-infrared (NIR) fluorescence molecular imaging to detect and evaluate the RA via the targeted fluorescence probes by quantitative analysis in this study.ResultsThe targeted fluorescence probes (indocyanine green-liposomes decorated with iRGD peptide [iLPs]) was successfully prepared. The quantitative analysis found that strong fluorescence signal was detected in inflamed paws and the fluorescence signal in iLPs group was 3.03-fold higher than that in non-targeted (indocyanine green-liposomes decorated without iRGD peptide [LPs]) group (P<0.01) at 15 min after injection, whereas the fluorescence signal from iLPs signal can almost not be observed in the non-inflamed paws, showing the high sensitivity and accuracy for arthritis by the NIR fluorescence imaging based on iLPs.ConclusionThe NIR fluorescence imaging by iLPs may facilitate improved arthritis diagnosis and early assessment of the disease progression by providing an in vivo characterization of angiogenesis in inflammatory joint diseases.

In vivo cellular-level real-time pharmacokinetic imaging of free-form and liposomal indocyanine green in liver.

Indocyanine green (ICG) is a near-infrared fluorophore approved for human use which has been widely used for various clinical applications. Despite the well-established clinical usage, our understanding about the microscopic in vivo pharmacokinetics of systemically administered ICG has been relatively limited. In this work, we successfully visualized real-time in vivo pharmacokinetic dynamics of the intravenously injected free-form and liposomal ICG in cellular resolution by utilizing a custom-built video-rate near infrared laser-scanning confocal microscopy system. Initial perfusion and clearance from blood stream, diffusion into perisinusoidal space, and subsequent absorption into hepatocyte were directly visualized in vivo. The quantification analysis utilizing the real-time image sequences revealed distinct dynamic in vivo pharmacokinetic behavior of free-form and liposomal ICG.

Optimization of liposomal indocyanine green for imaging of the urinary pathways and a proof of concept in a pig model.

Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging. Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R). The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60nm, which yielded a U/R of 5.2±1.7 (p<0.001 vs. free ICG). The optimal ICG dose was 8mg/kg (U/R=2.1±0.4, p<0.05 vs. 4mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10min after injection and persisting for at least 90min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection. Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments.

Liposomal Indocyanine Green for Enhanced Photothermal Therapy.

In this study, we engineered liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Various liposomal formulations of ICG were prepared by varying the lipid composition and the molar ratio between total lipid and ICG, and their photothermal characteristics were evaluated under near-infrared irradiation. We showed that the ICG dispersity in the liposomal membrane and its physical interaction with phospholipids were the main factors determining the photothermal conversion efficiency. In phototherapeutic studies, the optimized formulation of liposomal ICG showed greater anticancer effects in a mouse tumor model compared with other liposomal formulations and the free form of ICG. Furthermore, we utilized liposomal ICG to visualize the metastatic lymph node around the primary tumor under fluorescence imaging guidance and ablate the lymph node with the enhanced photothermal effect, indicating the potential for selective treatment of metastatic lymph node.

Intraoperative Localization of Rectal Tumors Using Liposomal Indocyanine Green.

Tumor localization may pose a significant challenge during minimally invasive rectal resection. Near-infrared (NIR) imaging can penetrate biological tissue and afford tumor localization from the external surface of the rectum. Our aim was to develop an NIR-based tool for rectal tumor imaging that can be administered intravenously. We prepared indocyanine-green (ICG)-loaded liposomes by sonication. Liposomes were evaluated for their size and morphology. We then used an endoscopically induced rectal cancer in mice as a model for rectal cancer. After intravenous administration, tumors were evaluated for their fluorescence intensity. Tumor intensity was expressed in relation to the background signal, that is, tumor to background ratio (TBR). Liposomes in various sizes could be prepared by adjusting sonication time. We selected 100-nm-sized liposomes for further experiments. Transmission electron microscopy showed spherical particles and confirmed the size measurements. The liposomes could be lyophilized and then rehydrated again before use without compromising their structure or signal. Fluorescence intensity was kept for 24 hours after solubilization. Testing the optimal time course for rectal tumor imaging revealed that early time course (up to 3 hours) yielded nonspecific imaging, whereas after long time course (24 hours), a very weak signal remained in the tissue. The optimal time window for imaging was after 12 hours from injection, with TBR = 8.1 ± 3.6 ( P = .002). Free ICG could not achieve similar results. The liposomal ICG can be reproducibly prepared and kept in lyophilized form. Liposomal ICG could serve as a tool for intraoperative tumor localization.

Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.

Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria.

Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naïve mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.

Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles

Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)-modified indocyanine green (ICG) liposomes (iRGD–ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to αvβ3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG2000-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD–ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of iRGD–ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy.