We report here a supramolecular strategy to directly assemble the small molecular hydrophobic anticancer drug camptothecin (CPT) into discrete, stable, well-defined nanostructures with a high and quantitative drug loading. Depending on the number of CPTs in the molecular design, the resulting nanostructures can be either nanofibers or nanotubes, and have a fixed CPT loading content ranging from 23% to 38%. We found that formation of nanostructures provides protection for both the CPT drug and the biodegradable linker from the external environment and thus offers a mechanism for controlled release of CPT. Under tumor-relevant conditions, these drug nanostructures can release the bioactive form of CPT and show in vitro efficacy against a number of cancer cell lines. This strategy can be extended to construct nanostructures of other types of anticancer drugs, and thus presents new opportunities for the development of self-delivering drugs for cancer therapeutics.

Cell penetrating peptides (CPPs) have been extensively explored as molecular vectors through covalent linkage to anticancer drugs to improve the drug’s water solubility and to help overcome multidrug resistance. We report here the use of the Tat CPP as a molecular building unit to construct well-defined supramolecular nanofibers that can be utilized as a nanoscale vector to encapsulate the hydrophobic drug paclitaxel (PTX) (loading efficiency: 89.7 ± 5.0%) with a high loading capacity (6.8 ± 0.4%). Notably, our TEM imaging results reveal that nanofibers containing a higher PTX content tend to be more flexible than those with a lower PTX content. Fluorescence and confocal microscopy imaging show that the Tat nanofibers can effectively transport encapsulated molecules into the cells through an adsorptive-mediated endocytosis pathway. Cytotoxicity experiments and flow cytometry measurements demonstrate that PTX loaded in the nanofibers exerts its cytotoxicity against cancer cells by arresting the cells at G2/M phase, the same working mechanism as free PTX.

During the coronavirus disease 2019 (COVID-19) outbreak in China, fear about COVID-19, together with worry about progression of cancer, caused strong emotional stress in patients with cancer. We evaluated patientreported outcome in 658 patients with breast cancer (BC) and survivors recruited from multiple BC centers in Hubei Province using 4 standardized assessment scales. Multivariable logistic regression analysis was used to identify potential affecting factors on mental health outcomes. High rates of anxiety, depression, distress, and insomnia were observed in patients with BC during the COVID-19 outbreak. Based on our results, living in Wuhan, poor general condition by self-identification, shorter duration after BC diagnosis, aggressive BC molecular subtypes, metastatic BC clinical stage, treatment discontinuation, central venous catheter flushing delay, or close contact with patients with COVID-19 are associated risk factors for poorer psychological status. Special attention should be paid to the psychological status of patients with BC, especially those with poor general condition, treatment discontinuation, aggressive molecular subtypes, and metastatic BC. Introduction: We aimed to analyze the psychological status in patients with breast cancer (BC) in the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Patients and Methods: A total of 658 individuals were recruited from multiple BC centers in Hubei Province. Online questionnaires were conducted, and these included demographic information, clinical features, and 4 patient-reported outcome scales (Generalized Anxiety Disorder Questionnaire [GAD-7], Patient Health Questionnaire [PHQ-9], Insomnia Severity Index [ISI], and Impact of Events Scale-Revised [IES-R]). Multivariable logistic regression analysis was designed to identify potential factors on mental health outcomes. Results: Questionnaires were collected from February 16, 2020 to February 19, 2020, the peak time point of the COVID-19 outbreak in China. Of patients with BC, 46.2% had to modify planned necessary anti-cancer treatment during the outbreak. Severe anxiety and severe depression were reported by 8.9% and 9.3% of patients, respectively.

Peptides or peptide conjugates capable of assembling into one-dimensional (1D) nanostructures have been extensively investigated over the past two decades due to their implications in human diseases and also their interesting applications as biomaterials. While many of these filamentous assemblies contain a β-sheet-forming sequence as the key design element, their eventual morphology could assume a variety of shapes, such as fibrils, ribbons, belts, or cylinders. Deciphering the key factors that govern the stacking fashion of individual β-sheets will help understand the polymorphism of peptide assemblies and greatly benefit the development of functional materials from customized molecular design. Herein, we report the decisive role of electrostatic interactions in the lamination and untwisting of 1D assemblies of short peptides. We designed and synthesized three short peptides containing only six amino acids (EFFFFE, KFFFFK, and EFFFFK) to elucidate the effective control of β-sheet stacking. Our results clearly suggest that electrostatic repulsions between terminal charges reduce the pitch of the twisting β-sheet tapes, thus leading to highly twisted, intertwined fibrils or twisted ribbons, whereas reducing this repulsion, either through molecular design of peptide with opposite terminal charges or through coassembly of two peptides carrying opposite charges, results in formation of infinite assemblies such as belt-like morphologies. We believe these observations provide important insight into the generic design of β-sheet assemblies.

Treatments of high specificity are desirable for cancer therapy. Light-triggered nanotheranostics (LTN) mediated cancer therapy could be one such treatment, as they make it possible to visualize and treat the tumor specifically in a light-controlled manner with a single injection. Because of their great potential in cancer therapy, many novel and powerful LTNs have been developed, and are mainly prepared from photosensitizers (PSs) ranging from small organic dyes such as porphyrin-and cyanine-based dyes, semiconducting polymers, to inorganic nanomaterials such as gold nanoparticles, transition metal chalcogenides, carbon nanotubes and graphene. Using LTNs and localized irradiation in combination, complete tumor ablation could be achieved in tumor-bearing animal models without causing significant toxicity. Given their great advances and promising future, we herein review LTNs that have been tested in vivo with a highlight on progress that has been made in the past a couple of years. The current challenges faced by these LTNs are also briefly discussed.

We report here the self-assembly of a rationally designed paclitaxel drug amphiphile into well-defined supramolecular filaments that possess a fixed 41% paclitaxel loading. These filaments can exert effective cytotoxicity against a number of cell lines comparable to that of free paclitaxel.

Intracellular sensing of pathologically relevant biomolecules could provide essential information for accurate evaluation of disease staging and progression, yet the poor cellular uptake of water-soluble molecular probes limits their use as protease sensors. In other cases such as extracellular sensing, cellular uptake should be effectively inhibited. Self-assembly of molecular probes into supramolecular nanoprobes presents a potential strategy to alter their interaction mechanisms with cells to promote or reduce their cellular uptake. Here, we report on the design, synthesis, and assembly of peptide-based molecular beacons into supramolecular protease sensors of either spherical or filamentous shapes. We found that positively charged spherical nanobeacons demonstrate much higher cellular uptake efficiency than its monomeric form, thus making them most suitable for intracellular sensing of the lysosomal protease cathepsin B. Our results also suggest that assembly into filamentous nanobeacons significantly reduces their internalization by cancer cells, an important property that can be utilized for probing extracellular protease activities. These studies provide important guiding principles for rational design of supramolecular nanoprobes with tunable cellular uptake characteristics.

Conjugation of anticancer drugs to hydrophilic peptides such as Tat is a widely adopted strategy to improve the drug’s solubility, cellular uptake and potency against cancerous cells. Here we report that attachment of an anticancer drug doxorubicin to the N- or C-terminal of the Tat peptide can have a significant impact on their cellular uptake, cytotoxicity against both drug-sensitive and drug-resistant cancer cells. We observed higher cellular uptake by both cell lines for C-terminal conjugate relative to the N-terminal analogue. Our results reveal that the C-terminal conjugate partially overcame the multi-drug resistance of cervical cancer cells, while the N-terminal conjugate showed no significant improvement in cytotoxicity when compared with free doxorubicin. We also found that both N- and C- conjugates offers a mechanism to circumvent drug efflux associated with multidrug resistance.