Enhancing Therapeutic Efficacy of Combined Cancer Phototherapy by Ultrasound‐Mediated In Situ Conversion of Near‐Infrared Cyanine/Porphyrin Microbubbles into Nanoparticles

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.

Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging

“…Additionally, in order to evaluate whether the inhibition of cell proliferation by PGL NPs and PGL-DOX NPs plus laser was due to its apoptotic effect, a live-dead assay of HeLa cells following uptake of NPs with and without laser irradiation was performed. This assay was conducted according to the previously described protocol 36 by Calcein-AM/PI double staining. In the experiment, the two control groups with and without laser irradiation and PGL NPs without laser irradiation did not reveal any dead cells (PI, red), as seen in Figure 7 C , but had almost all live cells showing green fluorescence (Calcein-AM, green).…”

Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

“…163,164 The design of supramolecular structures such as dendrimers, liposomes, microbubbles (MBs), polymers, micelles, films and inorganic NPs (silica, metals) are routinely investigated to enhance the penetration ability of deeply-suited tumours, phototherapeutic killing in vivo and other several combination therapies. 27,165,166 Recently, Zheng et al have summarized advancements in the design of porphyrin supramolecular chemistry for enhanced therapeutic outcomes. 139 For instance, higher therapeutic killing at a relatively low dose of porphyrin, long circulation time, excellent biocompatibility even at high dosing, and increased uptake by tumour cells were successfully validated by using different porphyrin-based supramolecular structures.…”

“…PTAs having imaging modalities can monitor the accumulation of NPs in tumours in real-time after systemic administration and provide guidance to PTT, which is called imaging-guided therapy. 33,207 Many imaging modalities, such as positron emission tomography (PET), [208][209][210] single photon emission computed tomography (SPECT), 211 MRI, [212][213][214] fluorescence imaging, 55,215 afterglow luminescence imaging, 216 PAI, 217 ultrasound imaging, 27,99,218 OCT, 219 and CT, 220,221 have been combined with PTAs to assist the conduction of therapies. 222 In some cases, multiple imaging modalities have been combined to provide more information for tumour diagnosis and therapy monitoring.…”

“…[23][24][25][26] In addition, nano PTAs can achieve higher PCE than small molecular PTAs and potentially integrate multiple imaging modalities and therapeutic functions into one platform for advanced applications. [27][28][29] In the following part of the review, PTAs are considered as nano PTAs unless otherwise stated. Tremendous efforts have been made toward improving the PTT performances, due to the presence of certain disadvantages or biological barriers that limit the effectiveness of PTT on cancer treatment.…”

Hydrogels: soft matters in photomedicine

“…438 Recent studies suggest that the combination of PDT and PTT could generate a synergistic therapeutic effect enhancing the efficacy of the overall treatment. 439 This synergism induces minor systematic toxicity, non-invasive characteristics and a higher selectivity, beyond the individual mode of treatments. 440 The effectiveness of both treatment modalities against tumors relies on the fact that both, the photosensitizer and photothermal agents, co-accumulate in the same target region.…”