Smart ¹³¹I‐Labeled Self‐Illuminating Photosensitizers for Deep Tumor Therapy

Abstract

Stimulating photosensitizers (PS) by Cerenkov radiation (CR) can overcome the light penetration limitation in traditional photodynamic therapy. However, separate injection of radiopharmaceuticals and PS cannot guarantee their efficient interaction in tumor areas, while co‐delivery of radionuclides and PS face the problem of nonnegligible phototoxicity in normal tissues. Here, we describe a 131I‐labeled smart photosensitizer, composed of pyropheophorbide‐a (photosensitizer), a diisopropylamino group (pH‐sensitive group), an 131I‐labeled tyrosine group (CR donor), and polyethylene glycol, which can self‐assemble into nanoparticles (131I‐sPS NPs). The 131I‐sPS NPs showed low phototoxicity in normal tissues due to aggregation‐caused quenching effect, but could self‐produce reactive oxygen species in tumor sites upon disassembly. Upon intravenous injection, 131I‐sPS NPs showed great tumor inhibition capability in subcutaneous 4T1‐tumor‐bearing Balb/c mice and orthotopic VX2 liver tumor bearing rabbits. We believed 131I‐sPS NPs could expand the application of CR and provide an effective strategy for deep tumor theranostics.

Cancer therapeutics based on diverse energy sources

“…52,54 Various studies have shown that CR can activate photosensitizers to generate ROS with several potential benefits compared with conventional PDT. 55–57 It can eliminate the need for external radiation, which can cause cellular damage. 53,54 Furthermore, after a systematic injection, many radiopharmaceuticals can accumulate specifically in tumors.…”

“…53,54 Furthermore, after a systematic injection, many radiopharmaceuticals can accumulate specifically in tumors. 56–59 Despite its advantages, this therapy also faces a difficult problem, namely, radioactive decay because radioisotopes decrease consistently in the absence of external and internal stimuli. Thus, the development of activatable sensitizers for cancer is essential to avoid off-target cytotoxicity.…”

“…9a). 56 The aggregation-caused quenching effect of the 131 I-sPS NPs resulted in modest phototoxicity in normal tissues, but upon disassembly, they could self-produce ROS in tumor regions. 131 I-sPS NPs inhibited tumor growth in subcutaneous and orthotopic animal models following intravenous administration.…”

Cerenkov radiation-activated probes for deep cancer theranostics: a review

“…We have developed a ZGC nanoplatform conjugated to 131 I-labeled ZnPc(COOH) 4 ( 131 I-ZGCs-ZnPcC4) that can support both radiotherapy as well as continuous, radiationinduced PDT through energy transfer from the ionizing radiation to ZGCs and then to ZnPc(COOH) 4 [95]. In another approach, we engineered pyropheophorbide-a containing PEG and a diisopropylamino group with an 131 I-labeled tyrosine, which self-assembled into pH-sensitive NPs [96]. These NPs exhibited minimal phototoxicity in normal tissue because of the quenched photodynamic effect, and under acidic conditions, they disassembled to promote the generation of ROS to achieve PDT and radiotherapy against deep-seated tumors (Figure 12A).…”

Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals

“…For instance, those superior cross-species translational abilities of rabbit myocardium may be relevant for the development and testing of novel cardiac sympathetic nerve systemtargeting therapies. Furthermore, the bigger organ size is a fundamental advantage for various biomedical assays including in vivo imaging technologies which have limited spatial resolution [10][11][12][13][14][15].…”