Targeted and imaging-guided in vivo photodynamic therapy for tumors using dual-function, aggregation-induced emission nanoparticles

Abstract

Imaging-guided photodynamic therapy (PDT) has been regarded as a promising strategy for precise cancer treatment. Because of their excellent modifiability and drug loading capacity, nanoparticles have played an important role in PDT. However, when traditional photosensitizers are made into nanoparticles, both their fluorescence and reactive oxygen species (ROS) generation efficiency are decreased due to a phenomenon known as aggregationcaused quenching. Fortunately, in recent years, several kinds of organic dyes have been developed with "abnormal" properties termed aggregation-induced emission (AIE). With enhanced fluorescence emission in the nano-aggregation state, the traditional obstacles mentioned above could be overcome by AIE luminogens (AIEgens). Herein, we provide a better combination of photosensitizers and nanoparticles, a kind of dual-functional AIE nanoparticle capable of producing ROS, to achieve targeted and imaging-guided in vivo PDT.Good contrast in in vivo imaging and obvious therapeutic efficiency were realized with a low dose of AIE nanoparticles as well as a low power density of light, resulting in negligible side effects. Our work demonstrates that AIE nanoparticles could play a promising role for imagingguided clinical photodynamic cancer therapy in the near future.Cancer has increasingly become a primary threat to human health, and more efficient treatment methods are urgently needed [1][2][3][4][5]. Conventional cancer treatment methods, including surgery, chemotherapy, and radiotherapy, lack accuracy and have significant side effects [6][7][8][9][10]. Thus, much attention has been paid to the development of alternative novel treatment modalities [11][12][13][14][15]. Imaging-guided photodynamic therapy (PDT) has been developed and shown to be an efficient, precise, and non-invasive medical technique for cancer therapy [16][17][18][19][20]. The photodynamic effect consists of three elements: a photosensitizer (PS), light of a suitable wavelength, and oxygen. Briefly, the energy of the light can be utilized to transfer the non-toxic triplet oxygen to toxic reactive oxygen species (ROS). Because the process occurs only when both the PS and light of a particular wavelength are present together, this method can provide good selectivity for the treatment region [21][22][23]. Meanwhile, most PSs demonstrate fluorescence emission [23,24], and with the guidance of fluorescence images, PDT can be a rather precise treatment modality.Along with the development of nanotechnology, various series of colloidal nanoparticles have become powerful tools in PDT [25][26][27][28]. Since the nanometer scale provides a high surfaceto-volume ratio, nanoparticles can ensure high drug-loading capacity as well as efficient surface chemical modification. A high drug-loading capacity leads to fewer side effects, while surface chemical modification allows for customized designs, which can greatly improve the specific properties of drugs, such as hydrophilicity [29], targeting ability [30][31][32][33] etc. In addition, ...

Aggregation‐Induced Emission: Recent Advances in Materials and Biomedical Applications

“…Due to the exceptional performance of AIE PSs, various AIE PS NPs have been reported for image‐guided PDT by concurrently utilizing their bright fluorescence and strong photosensitization . The first few generations of AIE PS NPs have demonstrated good performance for in vitro cancer cell ablation.…”

A new approach to developing diagnostics and therapeutics: Aggregation‐induced emission‐based fluorescence turn‐on

“…Sun et al fabricated tumor‐targeting NPs loaded with 14 (Figure ), which has an outstanding ability to produce ROS. The average size of the NPs was approximately 50 nm.…”

Nanoparticles-based photosensitizers with effect of aggregation-induced emission

“…To identify solid tumor cells the biosensor TPPP was proposed, which consisted of a PS PpIX and an AIE molecular TPE with PEGylated PLGVR peptide sequence as a linker [62]. When TPPP arrives at the tumor tissue, the overexpressed MMP-2 in tumor Based on AIEgen TPE-red with an outstanding ability to produce rOS performs the dualfunction AIE NPs for the purposeful and visual-guided PDT in vivo targeting UMUC3 cells (human bladder cancer cell line), HeLa (human cervical cancer cell line), and A549 (human lung carcinoma cell line) [63]. To enhance tumor targeting, promote endocytosis and ensure a therapeutic effect, the NPs were modified with a customized peptide, c(RGDfc), a group commonly used to target overexpressed integrin αvβ3 in most cancerous cells.…”