A macrophage exosome coated nanoplatform for targeted chemotherapy of triple-negative breast cancer.

In this paper, a three-dimensional (3D) cascaded lattice Boltzmann method (CLBM) is implemented to simulate the liquid-vapor phasechange process. The multiphase flow field is solved by incorporating the pseudopotential multiphase model into an improved CLBM, the temperature field is solved by the finite difference method, and the two fields are coupled via a non-ideal equation of state. Through numerical simulations of several canonical problems, it is verified that the proposed phase-change CLBM is applicable for both the isothermal multiphase flow and the liquid-vapor phase-change process. Using the developed method, a complete 3D pool boiling process with up to hundreds of spontaneously generated bubbles is simulated, faithfully reproducing the nucleate boiling, transition boiling, and film boiling regimes. It is shown that the critical heat flux predicted by the 3D simulations agrees better with the established theories and correlation equations than that obtained by two-dimensional simulations. Furthermore, it is found that with the increase in the wall superheats, the bubble footprint area distribution changes from an exponential distribution to a power-law distribution, in agreement with experimental observations. In addition, insights into the instantaneous and time-averaged characteristics of the first two largest bubble footprints are obtained.

Owing to the specific and high binding affinity of aptamers to their targets, aptamer−drug conjugates (ApDCs) have emerged as a promising drug delivery system for targeted cancer therapy. However, in a conventional ApDC, the aptamer segment usually just serves as a targeting moiety, and only a limited number of drug molecules are sequentially conjugated to the oligonucleotide, giving a relatively low drug loading capacity. To address this challenge, herein we employ four clinically approved nucleoside analogues, including clofarabine (Clo), ara-guanosine (AraG), gemcitabine (Ge), and floxuridine (FdU), to replace all natural nucleosides in aptamer sequences, generating a series of whole drug-constituted DNA-like oligomers that are termed drugtamers. Similar to their parent aptamers, the obtained drugtamers maintain the targeting capability and can specifically bind to the target receptors overexpressed on the cancer cell surface. With 100% drug loading ratio, active targeting capability, and enzymemediated release of active therapeutics, our drugtamers can strongly induce the apoptosis of cancer cells and inhibit the tumor progression, which enables a new potential for a better targeted cancer therapy.

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Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.