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Previous studies have showed promising but short-lived activity of sorafenib in osteosarcoma treatments. Researches have suggested ameliorated sensitivity to standard dose of conventional cancer therapies in combination with histone deacetylase inhibitors (HDACis) through various mechanisms. Herein, for the first time, we exploited the synergism of combination therapies with sorafenib and chidamide, a member of HDACis, in the control of OS using human OS cell lines and OS xenograft mouse model and discussed interactive mechanisms between the two drugs. The combination therapy exerted a strong synergism in the inhibition of OS cell proliferation, meanwhile prominently induced cell apoptosis and cell cycle arrest in G0/G1 phase in OS cells with increased expression of MCL-1, decreased expression of caspase-3 and P21, along with diminished level of the overlapped protein P-ERK1/2. Furthermore, oral administration of the combined treatment led to a more optical therapeutic outcome, including lower degrees of tumoral cell proliferation, greater extent of apoptosis, along with induction of cell cycle arrest in tumor tissues, while exhibiting minimal toxicity. This study shows that the combination of sorafenib and chidamide can combat OS in a synergistic fashion and prompts the promising development of innovative combined therapeutic strategies for OS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The overall survival rate of osteosarcoma (OS) patients has not been improved for 30 years, and the diagnosis and treatment of OS is still a critical issue. To improve OS treatment and prognosis, novel kinds of theranostic modalities are required. Molecular optical imaging and phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), are promising strategies for cancer theranostics that exhibit high imaging sensitivity as well as favorable therapeutic efficacy with minimal side effect. In this study, semiconducting polymer nanoparticles (SPN-PT) for OS-targeted PTT/PDT are designed and prepared, using a semiconducting polymer (PCPDTBT), providing fluorescent emission in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) signal in the first near-infrared window (NIR-I, 650 - 900 nm), served as the photosensitizer, and a polyethylene glycolylated (PEGylated) peptide PT, providing targeting ability to OS., Results: The results showed that SPN-PT nanoparticles significantly accelerated OS-specific cellular uptake and enhanced therapeutic efficiency of PTT and PDT effects in OS cell lines and xenograft mouse models. SPN-PT carried out significant anti-tumor activities against OS both in vitro and in vivo., Conclusions: Peptide-based semiconducting polymer nanoparticles permit efficient NIR-II fluorescence/NIR-I PA dual-modal imaging and targeted PTT/PDT for OS., (© 2022. The Author(s).)

Purpose: The small peptide TMTP1 (NVVRQ) has been proved to target a series of highly metastatic tumor cells. The aim of this study was to develop a new agent based on TMTP1 conjugated with Evans blue (EB), to increase tumor uptake and modify the pharmacokinetic characteristics of the resulting radiolabeled agent., Procedures: DOTA-EB-TMTP1 was prepared through conventional solid-phase peptide synthesis chemistry. Then, it was successfully labeled with Cu-64 to obtain [ 64 Cu]DOTA-EB-TMTP1. The tumor targeting properties were evaluated in vivo using 143B xenografts., Results: DOTA-EB-TMTP1 was successfully labeled with Cu-64 in a yield of 87.3 ± 5.2 %. In a small animal positron emission tomography/X-ray computed tomography (PET/CT) study in osteosarcoma 143B xenograft mice, [ 64 Cu]DOTA-EB-TMTP1 was found to rapidly accumulate in the tumor tissue. The tumor uptake increased over time and reached a plateau of 6.50 ± 0.88 % ID/g 8 h after tail vein injection. The radioactivity remained in the tumor tissue 48 h postinjection with a negligible decrease., Conclusions: Overall, the introduction of the EB motif to TMTP1 significantly changed its pharmacokinetics in vivo, and this strategy fulfills the purpose of prolonging the blood circulation and enhancing the tumor uptake. [ 64 Cu]DOTA-EB-TMTP1 is a promising agent for osteosarcoma targeting. Moreover, our study highlights that DOTA-EB-TMTP1 is a good candidate for labeling with different radionuclides for potential theranostic applications.

1064 nm laser activatable semiconducting polymer-based nanoparticles used as all-in-one phototheranostic nanoplatforms for dual-modal NIR-II fluorescence/NIR-II photoacoustic imaging-guided orthotopic tumoral treatment. [Display omitted] • All-in-one phototheranostic nanoplatform comprised of single-component semiconducting polymer-based nanoparticles. • Dual-modal NIR-II fluorescence/NIR-II photoacoustic imaging capability of solid tumor. • NIR-II activatable photothermal therapy in deep-seated orthotopic osteosarcoma. As a promising anti-tumoral approach, photothermal therapy (PTT) with NIR-II (1000–1700 nm) absorption could penetrate deeper and generate more efficient hyperthermia in contrast to traditional PTT under 808 nm irradiation. As for optical tracking, NIR-II fluorescence imaging (FI) and NIR-II photoacoustic imaging (PAI) are the two emerging research hotspots. Unfortunately, each single modality has its intrinsic limitations and current research to integrate them in one-component system is still in infancy. Our development of all-in-one nanoplatforms aims to ultimately improve the efficacy of targeted hyperthermia, and incorporate the benefits of NIR-II FI and NIR-II PAI for tracking guidance. Herein, we designed a novel semiconducting polymer P2, and further encapsulated it with amphiphilic PEGylated phospholipid modified with a targeting peptide RGD to ultimately generate P2 based nanoparticles (P2NPs). As a single-component phototheranostic nanoplatform, P2NPs possessed intense NIR-II absorption, excellent NIR-II fluorescence, strong NIR-II PA signals, and high local hyperthermia capability simultaneously. Notably, due to the favorable binding capacity to osteosarcoma (OS) cells, in vitro studies revealed outstanding PTT efficacy of P2NPs against 143B cells under 1064 nm laser. Further work validated excellent dual-modal NIR-II FI/NIR-II PAI tracking and strong PTT tumor ablation in both subcutaneous and orthotopic OS mice models with negligible biotoxicity in vivo. Consequently, these findings warranted P2NPs as a promising 1064 nm activatable all-in-one nanoplatform to perform dual-modal NIR-II FI/NIR-II PAI-guided orthotopic tumoral treatment, providing a new approach for theranostics, therapeutic tracking, and the beyond in other diseases. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s11307-021-01598-w [ABSTRACT FROM AUTHOR]