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Cancer ranks as a leading cause of death in every country of the world. However, if they are discovered early, a lot of cancers can be prevented or cured. Discovering and monitoring cancer markers are the main methods for early diagnosis of cancer. To date, many fluorescent probes designed and used for early cancer diagnosis can only react with a single marker, which always causes insufficient accuracy in complex systems. Herein, a novel near-infrared (NIR) fluorescent probe (CyO-DNP) for the sequential detection of H2S and H+ is synthesized. In this probe, a heptamethine dye is selected as the fluorophore and a 2,4-dinitrophenyl (DNP) ether is chosen as recognition group. In the presence of H2S, CyO-DNP is transformed into CyO, which exhibits an intense fluorescence at 663 nm. Then, H+ induces the protonation of CyO to obtain CyOH, and the final fluorescence emission at 793 nm significantly enhances. Owing to the low cytotoxicity and the NIR fluorescence emission, CyO-DNP can sequentially monitor endogenous H2S and H+ in cancer cells and image exogenous and endogenous H2S and H+ in mice. It is worth mentioning that CyO-DNP can effectively avoid the false positive signal caused by the liver and kidney and discriminate normal mice and tumor mice accurately. For all we know, CyO-DNP is the first fluorescent probe for early accurate diagnosis of cancer by sequentially detecting H2S and H+.

To develop a full-biodegradable thermoresponsive polymer with a wide temperature range, a hydrophilic, biodegradable and biocompatible thermoresponsive polymer having a polylactide backbone polymer and a side chain norbornene group was synthesized by ring-opening polymerization of a norbornene-functionalized lactide, followed by graft of backbone polymer with polyethylene glycol monomethyl ether (MPEG) and modification with isopropylamide (IPA), the latter of which critically influences the phase transition temperature of the copolymer. The effects of polymerization degree (DP), molecular weight of MPEG, the proportion of MPEG and IPA, and the concentration of polymer on the behaviors of the thermoresponsive polymer solution were systematically studied. The Cp ranged from 32 to 72 °C, and it was found that higher number of the MPEG moiety led to higher Cp, whereas the longer isopropylamide group resulted in lower Cp. It is noteworthy that with the unique characteristics, thermosensitivity at body temperature, biodegradability, and a well-defined copolymer structure, the developed thermoresponsive polymer is promising for biomedical applications as an essential material.

A near-infrared fluorescent probe, CyAc, is synthesized for accurately diagnosing cancer in vivo by sequential detection of Cys and H+. CyAc can not only discriminate normal cells and cancer cells, but also distinguish normal mice from tumor mice.

The traditional chemotherapy using single agent may suffer from serious drawbacks, particularly dose-limiting toxicity and relatively low antitumor efficacy, which can lead to failure of chemotherapy. Co-delivery of two or more therapeutic drugs in nanotechnology is a potential strategy to generate synergistic anticancer effects and reduce individual drug-related toxicity, but explosive release of each drug from multi-drug loaded nanoparticles has been a distinct obstacle. In this study, a novel amphiphilic and biodegradable triblock copolymer, named MPEG-b-norbornene functional PLA-b-P(α-BrCL), was constructed to covalently conjugate dual anticancer drugs, i.e., doxorubicin (DOX) and paclitaxel (PTX). The resultant P-PTX-DOX prodrugs were confirmed by 1H NMR and HPLC. By adjusting the length of PLA and PCL, it was shown that this polymer could carry relatively sufficient amount of both drugs (12.1 wt% of PTX and 15.8 wt% of DOX, respectively). Moreover, the drug release profile of P-PTX-DOX in vitro was also analyzed, which showed the desired drug release in a sustained manner. Cytotoxicity study indicated synergistic effects of P-PTX-DOX self-assembled micelles in suppression of proliferation of A549 cancer cells. In summary, a novel polyester-based copolymer was developed to covalently conjugate dual-drug, which exhibited controlled drug release behavior and synergistic anti-cancer efficacy in vitro.

Toxic hepatitis which is induced by chemical substance is a serious threat to human health. More and more studies have shown that peroxynitrite (ONOO−) is related with the development of toxic hepatitis. So it is important to find a tool to study ONOO− change during the diagnosis and therapy of toxic hepatitis. Herein, a series of novel near-infrared (NIR) fluorescence dyes (DDM-R) with long emission wavelength (740–770 nm) and large Stokes shift (~200 nm) are developed. Among the dyes, DDM-OH with great spectral performance and facilely modified feature is used to construct probe DDM-ONOO-. The probe have the preference of high sensitivity and excellent selectivity for ONOO−. In addition, DDM-ONOO- was applied in detecting exogenous and endogenous ONOO− in cells and further used in detecting ONOO− of CCl4-induced toxic hepatitis in cells by fluorescence imaging, 3D quantification analysis, flow cytometry. More importantly, by visualizing ONOO−, the probe was used to monitor the diagnosis of CCl4-induced toxic hepatitis in mice and evaluate the therapeutic efficacy of hepatoprotective medicines (NAC, SM, DDB). The results show that the probe will provide a powerful tool for the diagnosis and treatment of toxic hepatitis.

Early diagnosis of cancer is important to improve the chance of curing cancer. Intracellular pH plays a key role in many cellular events and is considered to be an important cancer marker. Unfortunately, near-infrared (NIR) fluorescence probe for detecting pH is rare. Herein, we designed and synthesized a pH NIR fluorescence probe termed CyO for cancer diagnosis. The acidic environment induces the protonation of CyO to form CyOH, resulting in fluorescence enhancement in NIR region. When pH varies from 7.4 to 5.0, the near-infrared fluorescence is increased by 20-fold. And there is a good linear relationship between fluorescence intensity and pH. In particular, the NIR fluorescence probe is applied for discriminating between normal and cancer environment by the detection of pH in various biological samples such as cell, tissue and living animal. This provides basic information that is helpful in early diagnosis of cancer.