Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

Photodynamic therapy suffers from poor tumor selectivity and poor therapeutical efficacy. In this paper, an amphiphilic chimeric peptide is fabricated to realize sequential acidity‐responsive tumor‐targeted transport of photosensitizer and in situ photodynamic therapy in nuclei. In vitro studies demonstrate that the acidic tumor microenvironment successfully sheds the mask of cationic nuclear localization sequence (NLS) of the negatively charged chimeric peptide. This charge reversal remarkably accelerates cellular uptake of chimeric peptide in tumor cells and maximizes the photodynamic therapeutical efficacy in nuclei. Most importantly, direct disguise of the biofunctional NLS sequence decreases the complexity and increases the performance of the chimeric peptide further by achieving long blood retention time, specific tumor accumulation, minimal side effects, and efficient antitumor therapy in vivo.

Cigarette smoking is a major pathogenic factor in lung cancer. Macrophages play an important role in host defense and adaptive immunity. These cells display diverse phenotypes for performing different functions. M2 type macrophages usually exhibit immunosuppressive and tumor-promoting characteristics. Although macrophage polarization toward the M2 phenotype has been observed in the lungs of cigarette smokers, the molecular basis of the process remains unclear. In this study, we evaluated the possible mechanisms for the polarization of mouse macrophages that are induced by cigarette smoking (CS) or cigarette smoke extract (CSE). The results showed that exposure to CSE suppressed the production of reactive oxygen species (ROS) and nitric oxide (NO) and down-regulated the phagocytic ability of Ana-1 cells. The CD163 expressions on the surface of macrophages from different sources were significantly increased in in vivo and in vitro studies. The M1 macrophage cytokines TNF-α, IL-12p40 and enzyme iNOS decreased in the culture supernatant, and their mRNA levels decreased depending on the time and concentration of CSE. In contrast, the M2 phenotype macrophage cytokines IL-10, IL-6, TGF-β1 and TGF-β2 were up-regulated. Moreover, phosphorylation of JAK2 and STAT3 was observed after the Ana-1 cells were treated with CSE. In addition, pretreating the Ana-1 cells with the STAT3 phosphorylation inhibitor WP1066 inhibited the CSE-induced CD163 expression, increased the mRNA level of IL-10 and significantly decreased the mRNA level of IL-12. In conclusion, we demonstrated that the M2 polarization of macrophages induced by CS could be mediated through JAK2/STAT3 pathway activation.

Gold nanoparticles (AuNPs) exhibit great potential for biological applications due to their good biocompatibility and tunable localized surface plasmon resonance (LSPR) properties. Currently, although tuning the aspect ratio of a solid structure or designing a hollow structure has been performed to regulate the LSPR properties of AuNPs, the method of preparing hollow anisotropic AuNPs has rarely been reported. In this study, we designed gold hollow nanorods (AuHNRs) with controllable aspect ratios by a Se-doping Te nanorod-templated method with the assistance of L-cysteine. UV−vis−NIR spectra showed that AuHNRs with an aspect ratio of about 3 could have a LSPR peak in the second near-infrared (NIR-II) window, which is only half of the value required by traditional Au nanorods. Moreover, AuHNRs are nontoxic and capable of loading drugs. In vivo experiment revealed that AuHNRs can be used as contrast agents in multimodal imaging, including photothermal imaging, photoacoustic imaging, and computed tomography imaging, as well as in chemo-photothermal combined therapy of tumor in the NIR-II window. Because light in the NIR-II window has remarkable advantages over that in the first near-infrared (NIR-I) window in biomedical applications, AuHNRs can be used as promising NIR-II-window-responsive multifunctional nanoagents.

Cancer is a major public health issue, with metastatic cancer accounting for the overwhelming majority of cancer deaths. Early diagnosis and appropriate treatment of metastatic cancer may largely prolong the survival rate and improve the quality of life for patients. In this study, we have identified a panel of DNA aptamers specifically binding to MDA-MB-231 cells derived from metastatic site-pleural effusion, with high affinity after 15 rounds of selections using the cell-based systematic evolution of ligands by exponential enrichment (SELEX) method. The selected aptamers were subjected to flow cytometry and laser confocal fluorescence microscopy to evaluate their binding affinity and selectivity. The aptamer LXL-1 with the highest abundance in the enriched library demonstrated a low K(d) value and excellent selectivity for the recognition of the metastatic breast cancer cells. Tissue imaging results showed that truncated aptamer sequence LXL-1-A was highly specific to the corresponding tumor tissue and displayed 76% detection rate against breast cancer tissue with metastasis in regional lymph nodes. Therefore, on the basis of its excellent targeting properties and functional versatility, LXL-1-A holds great potential to be used as a molecular imaging probe for the detection of breast cancer metastasis. Our result clearly demonstrates that metastatic-cell-based SELEX can be used to generate DNA ligands specifically recognizing metastatic cancer cells, which is of great significance for metastatic cancer diagnosis and treatment.