The development of biocompatiable efficient photothermal coupling agent (PCA) for image-guided photothermal therapy of cancer has gained increasing interests in recent years. Although various PCAs have been developed, the clinical translations of these materials have been largely hindered by the potential biosafety issues and challenges of scaling-up manufactures. In this research, we proposed nano-sized indocyanine green (ICG) J-aggregate (IJA) as a promising PCA which is fabricated by a very facile method using clinical-approved ICG as the only excipient. The as-prepared IJA remains stable in various solution and shows a ~115 nm red-shift in absorption peak compared to free ICG. Importantly, IJA can be disassociated into free ICG again after internalized into cells and exhibits high biosafety comparable to ICG. The IJA performs well for photothermal therapy both in vitro and in vivo. In addition, the IJA can also be used as a good photoacoustic contrast agent and internalization-responsive fluorescence probe. The facile preparation, high safety and excellent theranostic performance indicated that IJA might be a promising one-component agent for cancer theranostics.

Rationale: Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD. Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form.Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD).Results: The liposomal nanohybrid cerasome exhibited superior stability towards PS 80 surfactant solubilization and longer circulation lifetime (t1/2 = 6.22 h), much longer than free curcumin (t1/2 = 0.76 h). The permeation was found to be 1.7-fold higher than that of CPC treatment only at 6 h after the systemic administration of CPC NPs. Notably, motor behaviors, dopamine (DA) level and tyrosine hydroxylase (TH) expression all returned to normal, thanks to α-synuclein (AS) removal mediated by efficient curcumin delivery to the striatum. Most importantly, the animal experiment demonstrated that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice had notably improved behavior disorder and dopamine depletion during two-week post-observation after treatment with CPC NPs (15 mg curcumin/kg) coupled with UTMD.Conclusion: This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future.

No abstract

Inflammation is an immunological response involved in various inflammatory disorders ranging from neurodegenerative diseases to cancers. Luminol has been reported to detect myeloperoxidase (MPO) activity in an inflamed area through a light-emitting reaction. However, this method is limited by low tissue penetration and poor spatial resolution. Here, we fabricated a nanobubble (NB) doped with two tandem lipophilic dyes, red-shifting luminol-emitted blue light to near-infrared region through a process integrating bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). This BRET–FRET process caused a 24-fold increase in detectable luminescence emission over luminol alone in an inflammation model induced by lipopolysaccharide. In addition, the echogenicity of the BRET–FRET NBs also enables perfused tissue microvasculature to be delineated by contrast-enhanced ultrasound imaging with high spatial resolution. Compared with commercially available ultrasound contrast agent, the BRET–FRET NBs exhibited comparable contrast-enhancing capability but much smaller size and higher concentration. This bioluminescence/ultrasound dual-modal contrast agent was then successfully applied for imaging of an animal model of breast cancer. Furthermore, biosafety experiments revealed that multi-injection of luminol and NBs did not induce any observable abnormality. By integrating the advantages of bioluminescence imaging and ultrasound imaging, this BRET–FRET system may have the potential to address a critical need of inflammation imaging.

The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy. In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy.Methods: A relatively simple and inexpensive rapid injection method was used to prepare porphyrin-grafted lipid (PGL) NPs. The self-assembled PGL NPs were used further to encapsulate DOX via a pH-gradient loading protocol. The self-assembled liposome-like PGL NPs having a hydrophilic core were optimized to load DOX at an encapsulation efficiency (EE) of ~99%. The resultant PGL-DOX NPs were intact, highly stable and importantly these NPs successfully escaped from the endo-lysosomal compartment after laser irradiation to release DOX in the cytosol. The therapeutic efficacy of the aforementioned formulation was validated both in vitro and in vivo.Results: PGL-DOX NPs demonstrated excellent cellular uptake, chemo-photodynamic response, and fluorescence imaging ability in different cell lines. Under laser irradiation, cells treated with a low molar concentration of PGL-DOX NPs reduced cell viability significantly. Moreover, in vivo experiments conducted in a xenograft mouse model further demonstrated the excellent tumor accumulation capability of PGL-DOX NPs driven by the enhanced permeability and retention (EPR) effect. Through fluorescence imaging, the biodistribution of PGL-DOX NPs in tumor and major organs was also easily monitored in real time in vivo. The inherent ability of porphyrin to generate ROS under laser irradiation combined with the cytotoxic effect of the anticancer drug DOX significantly suppressed tumor growth in vivo.Conclusion: In summary, the PGL-DOX NPs combined chemo-photodynamic nanoplatform may serve as a potential candidate for cancer theranostics.

No abstract

Nanoparticles (NPs)-based diagnosis and phototherapy are emerging as the cutting-edge technologies for detection and treatment of cancer but their applications are still limited since insufficient and heterogeneous NPs accumulation in cancer often causes recurrence. To overcome these limitations, multifunctional microbubbles (MBs) were constructed with 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindotricarbocyanine iodide (DiR) and porphyrin grafted lipid (PGL). Both DiR and PGL self-assembled as microbubbles, the as-designed PGL-DiR MBs possess remarkably high drug loading contents (5.8% PGL and 10.38% DiR) and stable co-delivery drug combinations. In vivo experiments showed PGL-DiR MBs could serve as an excellent ultrasound contrast agent to enhance ultrasound imaging greatly for identifying the location and size of the tumors. Upon exposure to ultrasound, in situ conversion of PGL-DiR MBs into nanoparticles resulted in a remarkable increase in fluorescence intensity (~5 folds) in tumor compared with PGL-DiR NPs, validating the enhanced tumor accumulation and cellular uptake of therapeutic agents. PGL-DiR MBs showed complete tumor ablation without recurrence in vivo, while PGL-DiR NPs showed only 72.6% tumor growth inhibition at the same dose. We believe that PGL-DiR MBs will soon reach their full potential as an important class of phototherapeutic formulations and will contribute to remarkable advances in cancer treatments.

The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade. Only a few nontargeted dyes, including indocyanine green and methylene blue, are currently applied for fluorescence guided surgery in the clinic. While no targeted fluorescent probes have been approved for the clinic, a number of them have entered clinical trials. These probes have emission wavelengths in the visible and near infrared (NIR)‐I (700‐900 nm) range. Among them, activatable probes and nanoprobes have generated special interest. Compared with NIR‐I fluorescent probes, NIR‐II (1000‐1700 nm) fluorescent probes exhibit better intravital performance in terms of increased penetration depths, reduced tissue autofluorescence, and higher signal‐to‐background ratios. However, more challenges are expected before the successful translation of NIR‐II probes from bench to bedside. This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR‐II fluorescence imaging. In addition, we outline key considerations concerning the design of fluorescent probes for clinical translation.