Although drug delivery based on nanomaterials has shown great potential in practical applications, the trans-membrane mechanism of the drug carrier is still unclear due to technical limitations. Here, we report the dynamic transporting process of a single dendritic polyamidoamine particle via cell membranes in real time by the force tracing technique.

Carbonized polymer dots (CPDs), as a novel fluorescent material, have broad application prospects in the fields of bio-imaging, bio-sensors, disease diagnosis and photovoltaic devices due to their low cost, low toxicity, easy modification and little environmental impact. In this paper, folic acid (FA) modified CPDs (FA-CPDs) are synthesized from p-Phenylenediamine (p-PD) and FA molecules using a traditional one pot hydrothermal reaction in order to detect cancer cells containing a folate receptor (FR). The synthesized FA-CPDs were characterized by transmission electron microscopy, Fourier transfrom infrared spectroscopy, x-ray photoelectron spectroscopy, x-ray diffraction, UV–vis and fluorescence techniques. The red fluorescence emission is realized by doping phosphorus atoms into the carbonized polymer. Upon excitation at 513 nm, the maximum emission wavelength of FA-CPDs aqueous solution was obtained at 613 nm. Moreover, the as-prepared FA-CPDs exhibit excellent excitation-independent behavior and good stability with high quantum yield (QY) at about 30.6%. The binding of FA-CPDs with FRs on cancer cells produces target recognition and enters the cells through endocytosis. Additionally, it is worth noting that FA-CPDs have good biocompatibility and imaging in HeLa cells has been successfully achieved. Therefore, our FA-CPDs have potential applications as biocompatibility probes for cancer diagnosis and treatment.

Considerable technological success has been achieved in the drug delivery of nano-drugs for chemotherapy, but the main obstacles in understanding the drug delivery dynamic mechanisms for nano-drug applications stem from technical limitations. In this paper, we explored the trans-membrane dynamic processes of polyamidoamine nano-drugs via a "force tracing" technique.Nanocarriers have been used as intelligent drug delivery systems (DDSs) to signicantly improve the bioavailability of poorly soluble drugs and the efficacy of drugs for clinical treatment.1-6 Among the many nanocarriers, polyamidoamine (PAMAM) dendrimers undoubtedly show a superior performance, attracting researchers' attention, 7 since they have the advantages of non-immunogenicity and a high transport efficiency for carrying bioactive agents.8 In addition, as PAMAM is sensitive to pH, the drug can be released from the interior of the macromolecule via diffusion, so as to achieve a sustained release and enhance the drug efficacy. In contrast to other nanocarriers, PAMAM dendrimers are highly branched synthetic macromolecules obtained via iterative stepwise reaction sequences, 9 and the highly branched structure ensures the facile modication of the dendrimer nanoparticle surface with different therapeutic drugs, diagnostic agents, and targeting ligands.10 The branched structure also makes it easy to conjugate with uorescein isothiocyanate for imaging live cells and tracking the drug carriers.11 The internal molecular cavity of PAMAM provides the ability to physically encase small molecule drugs through electrostatic interactions and/or hydrogen bonding interactions. 12Usually, covalent conjugation and encapsulation are the main methods for loading drugs on PAMAM. E. W. Meijer and coworkers reported that guest molecules were captured within the internal cavities of the dendritic nanoparticles, and that the diffusion of guest molecules out of the carriers into solution was slow because of the close packing of the shell.13 In order to understand the effect of drug loading on the structural properties of the dendrimer, V. Jain et al. used molecular dynamic (MD) simulations to characterize the molecular models of dendrimer-nateglinide encapsulation complexes, and the MD analysis revealed that both the pH value of the solution and the terminal groups of the dendrimer play a part in drug encapsulation efficiency.14 Another effective approach used in drug loading is the covalent conjugation of the drug to the terminal functional groups of the dendrimers.12 Y. Gao et al. successfully conjugated ursolic acid (UA) and folic acid (FA) to PAMAM, and a subsequent cellular uptake study indicated that the presence of FA enhanced the uptake of dendrimeric prodrugs by HeLa cells with over-expressed folate receptors (FRs). This effect could be attributed to FR-mediated endocytosis.15 R. Mohammad et al. developed PAMAM-pullulan conjugates and investigated their targeting activity in delivering genes into liver cells. Furthermore, they assessed the cytotoxicity and tra...

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