Dendritic Polymers for Theranostics

Abstract

Dendritic polymers are highly branched polymers with controllable structures, which possess a large population of terminal functional groups, low solution or melt viscosity, and good solubility. Their size, degree of branching and functionality can be adjusted and controlled through the synthetic procedures. These tunable structures correspond to application-related properties, such as biodegradability, biocompatibility, stimuli-responsiveness and self-assembly ability, which are the key points for theranostic applications, including chemotherapeutic theranostics, biotherapeutic theranostics, phototherapeutic theranostics, radiotherapeutic theranostics and combined therapeutic theranostics. Up to now, significant progress has been made for the dendritic polymers in solving some of the fundamental and technical questions toward their theranostic applications. In this review, we briefly summarize how to control the structures of dendritic polymers, the theranostics-related properties derived from their structures and their theranostics-related applications.

Keywords: Dendritic polymers; theranostics.

Figure 1

Schematic description of six subclasses of dendritic polymers.

Figure 2

Schematic structures of biodegradable or biocompatible dendritic polymers. (a) DNA dendrimer , (b) hyperbranched peptide , (c) hyperbranched glycopolymer , (d) hyperbranched polyphosphate , (e) hyperbranched polyamide , (f) dendritic polyglycerol .

Figure 3

Schematic illustration of various stimuli including internal different index and external stimuli.

Figure 4

Schematic illustration of various topological structures self-assembled from dendritic polymers with different size scales.

Figure 5

(A) Schematic illustration of polyprodrug unimolecular micelles with hyperbranched cores conjugated with gadolinium complex, reductive milieu-cleavable camptothecin prodrugs and hydrophilic coronas functionalized with guanidine residues. (B) T₁-weighted spin-echo MR images of (a) small molecule alkynyl-DOTA(Gd) (DOTA, tetraazacyclododecanetetraacetic acid) complex and hyperbranched polyprodrug amphiphilies (HPA) after incubating with various concentrations of DL-dithothreito (DTT) for 12 h. (C) Water proton longitudinal relaxation rates (1/T₁) of small molecule alkynyl-DOTA(Gd) complex and HPA after treating with DTT (0-20 mM). (D) MR images recorded for (a) untreated HepG2 cells, (b) HepG2 cells treated with HPA for 12 h, and (c) HepG2 cells pretreated with 10 mM GSH-OEt (GSH reduced ethyl ester) for 2 h to elevate intracellular GSH level, and then coincubated with HPA for 12 h. Reprinted with permission from ref. 77. Copyright 2015, American Chemical Society.

Figure 6

(A) Synthesis route of HCP-N-PEG (pH-responsive polymer, in which HCP and PEG were conjugated with acyldydrazone linkage) and HCP-O-PEG (non-responsive polymer, in which HCP and PEG were conjugated with ether linkage) star-conjugated copolymers. (B) Self-assembly of star-conjugated copolymer and their endocytosis in the tumor cells. (C, D) Time-dependent fluorescence microscope images of MCF-7 cells incubated with DOX-loaded HCP-N-PEG (C) and HCP-O-PEG (D) micelles. Reproduced with permission from ref. 15. Copyright 2014, American Chemical Society.

Figure 7

(A) Chemical structures of the four polymers examined: a cationic dendronized poly-(3,5-bis(3-aminopropoxy)benzyl)-methacrylate (PG1), cationic ɑ-poly(D-lysine) (PDL), neutral methoxy PEG (mPEG) and anionic poly(acrylic acid) (PAA). (B) The uncleaved peptide substrate was incubated in vitro with MX, MX-polymer conjugates or endogenous enzymes. All MX-polymer conjugates induced a significant increase in fluorescence intensity after peptide cleavage. (C) The activity of the individual MX-polymer conjugates was measured using an in vivo fluorescence assay. Reproduced with permission from ref. 119. Copyright 2013, Nature Publishing Group.

Figure 8

(A) Chemical structures of the parent silicon naphthalocyanine. (B) Schematic illustration of the fabrication of SiNc-loaded theranostic nanoplatform. Reproduced with permission from ref. 138. Copyright 2015, Royal Society of Chemistry.

Figure 9

(A) Synthetic route of CH12-HPSA-¹⁸⁸Re. (B) The biodistribution of CH12-HPSA-¹⁸⁸Re in nude mice was determined by SPECT. The gamma images were acquired at 1, 6, 24, 48 h after tail vein injection, respectively. (Black arrow: tumor area). Reproduced from ref. 148.