Understanding the cellular uptake of nanomaterials (NMs) is a fundamental and critical issue for uncovering biomedical effects of NMs and facilitating their practical applications in the clinic. In this Review, by highlighting the differences of NMs cellular uptake between in vitro and in vivo, a focus on reviewing recent works about the effects of four physicochemical parameters of NMs (size, rigidity, shape, surface modification) on regulating NMs cellular uptake in vitro and in vivo is undertaken. This review can provide readers some useful clues and new thinking for understanding NMs cellular uptake in depth.

One of the biggest obstacles for the development of HIV vaccines is how to sufficiently trigger crucial anti-HIV immunities via a safe manner. We herein integrated surface modification-dependent immunostimulation against HIV vaccine and shape-dependent biosafety and designed a safe noncarrier adjuvant based on silver nanorods coated by both polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). Such silver nanorods can significantly elevate crucial immunities of HIV vaccine and overcome the toxicity, which is a big problem for other existing adjuvants. This study thus provided a principle for designing a safe and high-efficacy material for an adjuvant and allow researchers to really have a safe and effective prophylaxis against HIV. We expect this material approach to be applicable to other types of vaccines, whether they are preventative or therapeutic.

Nanoscale materials can improve the efficacy of vaccines. Herein we review latest developments that use nanomaterials for vaccines. By highlighting the relationships between the nanoscale physicochemical characteristics and working mechanisms of nanomaterials, this paper shows the current status of the developments where researchers employ functional nanomaterials as vector and/or immunoregulators for vaccines. It also provides us some clues for improving the design and application of nanomaterials to optimize the efficacy of vaccines.

Polymer-based fluorescent nanomaterials have proven to universally image various tumors based on their extremely sharp responsiveness to pH change. Such a property has never been realized in supramolecular systems. We herein design a small molecule (DPP-thiophene-4) that is composed of a diketopyrrolopyrrole (DPP) core and two alkyl chains terminated with quaternary ammonium. DPP-thiophene-4 can self-assemble into a nonfluorescent nanoassembly when the pH is >7.0 but reversibly disassembles back to fluorescent monomers when the pH is <6.8. Meanwhile, its fluorescence emission increases by 10-fold within a 0.2 pH unit change. Such a fluorogenic nanoassembly can precisely differentiate a number of malignant tumors among normal tissues in vivo due to the slight acidity within tumor microenvironments. Further the nanoassembly shows satisfactory biocompatibility and an effective clearance from the body. Overall, this supramolecular fluorogenic nanoassembly exhibits an immense potential for realizing broad range tumor diagnosis.

Intermolecular forces constrain peptide conformation. However, the role of each intermolecular force in constraining peptide conformation remains poorly understood. In this work, we show that aromatic–aromatic interactions drive peptides into β‐sheets, and the hydrophobic effect determines the assembly speed of peptides. By using intermolecular forces to artificially control the assembly of β‐sheets, a multi‐modal analytical system was developed that allows five readouts and dual qualitative–quantitative analysis, and satisfies both point‐of‐care testing (POCT) and laboratory‐based testing. For Mycoplasma Pneumoniae diagnosis, this system eradicates misdiagnosis (from 30 % to 0 %) and broadens the linear range by three‐fold, both of which are critical for guiding therapy. This work not only illustrates exact roles of intermolecular forces in driving the formation of β‐sheets, but also provides a guideline for the construction of a multi‐modal analytical system for disease diagnosis.