ABSTRACT
Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.
ABSTRACT
Hybridized periodic mesoporous organosilica (PMO) nanoparticles are expected to provide a multifunctional theranostic platform for precision medicine by combining the advantages of different organic and inorganic components. In this work, double-shell-structured PMO nanotheranostics composed of ethane- and thioether-bridged organosilica shells were synthesized. Gold colloids were generated in situ by the thioether groups on the inner shell. The obtained double-shell PMO@Au (DSPA) has uniform size, large surface areas, ordered mesochannels and photothermal conversion capability. After being encapsulated with perfluorohexacene (PFH), DSPA-PFH produced a strong ultrasound signal upon laser irradiation due to the phase transit of PFH during hyperthermia. DSPA-PFH showed enhanced photothermal therapeutic efficacy, great ultrasound contrast, and minimal toxicity both in vitro and in vivo. These results demonstrated the distribution of different organosilica could be delicately adjusted in hybridized PMO nanoparticles. Furthermore, it showed the potential of using hybridized PMO nanoparticles as a theranostic platform for biomedical applications by combining unique characteristics of different organosilica through rational design.
Subject(s)
Nanoparticles , Theranostic Nanomedicine , Photothermal Therapy , UltrasonographyABSTRACT
Intratumoral nanoparticles (NPs) distribution is critical for the success of nanomedicine in imaging and treatment, but computational models to describe the NPs distribution remain unavailable due to the complex tumor-nano interactions. Here, we develop a Generative Adversarial Network for Distribution Analysis (GANDA) to describe and conditionally generates the intratumoral quantum dots (QDs) distribution after i.v. injection. This deep generative model is trained automatically by 27,775 patches of tumor vessels and cell nuclei decomposed from whole-slide images of 4 T1 breast cancer sections. The GANDA model can conditionally generate images of intratumoral QDs distribution under the constraint of given tumor vessels and cell nuclei channels with the same spatial resolution (pixels-to-pixels), minimal loss (mean squared error, MSE = 1.871) and excellent reliability (intraclass correlation, ICC = 0.94). Quantitative analysis of QDs extravasation distance (ICC = 0.95) and subarea distribution (ICC = 0.99) is allowed on the generated images without knowing the real QDs distribution. We believe this deep generative model may provide opportunities to investigate how influencing factors affect NPs distribution in individual tumors and guide nanomedicine optimization for molecular imaging and personalized treatment.
Subject(s)
Breast Neoplasms , Nanoparticles , Breast Neoplasms/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Reproducibility of ResultsABSTRACT
Immunotherapy is a major emerging treatment for breast cancer (BC). However, not all breast cancer patients derive benefit from immunotherapy. Predictive biomarkers of immunotherapy, such as tumor mutation burden and tumor-infiltrating lymphocytes, are promising to stratify the patients with BC and optimize the therapeutic effect. Various targets of the immune response pathway have also been explored to expand the modalities of immunotherapy. The use of nanotechnology for the imaging of predictive biomarkers and the combination with other therapeutic modalities presents a number of advantages for the immunotherapy of BC. In this review, we summary the emerging therapeutic modalities of immunotherapy, present prominent examples of immunotherapy in BC, and discuss the future opportunity of nanotechnology in the immunotherapy of BC.
ABSTRACT
Despite transition metal phosphide (TMP)-based hybrid structures demonstrating desirable results for potassium ion battery applications, most of their preparation methods require complex multi-step procedures. Herein, a three-dimensional (3D) structural material in which amorphous carbon (AC) encapsulated CoP nanoparticles are embedded at the top of nitrogen-doped carbon nanotubes derived from ZIF-67/ZIF-8 grown on the surface of carbon nanofibers (AC@CoP/NCNTs/CNFs) is reported for the first time. The CoP acts as a core and the amorphous carbon layer acts as a shell, which restrains the volume expansion of active materials during charging and discharging. Furthermore, the carbon nanofiber network can improve the conductivity, and doped nitrogen can increase active sites. As a result, the electrochemical properties of the potassium ion battery are enhanced when an AC@CoP/NCNTs/CNFs nanocomposite is used as the anode electrode, and the electrode exhibits a reversible capacity of 247â¯mAâ¯hâ¯g-1 after 1000 cycles at 0.8â¯Aâ¯g-1 in a potassium ion battery.