A positron emission tomography image-guidable unimolecular micelle nanoplatform for cancer theranostic applications.

摘要: Abstract Unimolecular micelles based on hyperbranched polyamidoamine (PAMAM) dendrimer were synthesized as both a cargo delivery vector and an imaging agent for triple-negative breast tumors, the chemical synthesis procedures are detailed in this study. With conjugation of peptide (F3, against cellular nucleolin) to increase its internalization, these can accumulate potently specifically cancer cells (e.g., MDA-MB-231). The size morphology PAMAM-based have been measured by transmission electron microscopy (TEM) dynamic light scattering (DLS). hydrazone bond (responsive pH alteration) between loaded doxorubicin (DOX, model drug here) PAMAM enables release following changes. Flow cytometry confocal fluorescence revealed that with F3 attachment (PAMAM-DOX-F3) had stronger internalization into MDA-MB-231 (nucleolin-positive) than without (PAMAM-DOX), whereas them minimal interactions L929 fibroblasts (nucleolin-negative). positron-emitting isotope 64Cu was added chelation track their pharmacokinetic behavior (organ distribution profile) vivo positron emission tomography (PET) imaging. Serial PET demonstrated accumulation 64Cu-PAMAM-DOX-F3 tumors fast, potent, persistent (tumor uptake: 6.1 ± 1.2% injection dose per gram [%ID/g] at 24 h p.i.), significantly higher 64Cu-PAMAM-DOX (2.5 ± 0.4%ID/g same time). Their profiles other organs/tissues quite similar, relatively short circulation time. In addition, ex confirmed DOX be delivered efficiently tumors. Deducing from data, we believe useful selective combinational treatment cancer. Statement Significance Micelles very biomaterial theranostic purposes, one major hurdles (particularly those self-assembling) is low stability, especially when administered vivo. study, attempted overcome limitation designing unimolecular (based concept “one micelle composed macromolecule”) dendrimers, which cargos doxorubicin) chemically attached through bond; hence, they used tumor-selective diagnostic/therapeutic platform. These possess superior stability compared conventional undertake stimulus (pH)-responsive more “targeted” therapy. incorporation tumor-targeting sequence (F3) (copper-64), readily monitored technique confirm specificity tissues. further optimization, micellar platform broad clinical applicability owing biocompatibility, selectivity, stability.