Polymerization-Induced Self-Assembly for Efficient Fabrication of Biomedical Nanoplatforms

Abstract

Amphiphilic copolymers can self-assemble into nano-objects in aqueous solution. However, the self-assembly process is usually performed in a diluted solution (<1 wt%), which greatly limits scale-up production and further biomedical applications. With recent development of controlled polymerization techniques, polymerization-induced self-assembly (PISA) has emerged as an efficient approach for facile fabrication of nano-sized structures with a high concentration as high as 50 wt%. In this review, after the introduction, various polymerization method-mediated PISAs that include nitroxide-mediated polymerization-mediated PISA (NMP-PISA), reversible addition-fragmentation chain transfer polymerization-mediated PISA (RAFT-PISA), atom transfer radical polymerization-mediated PISA (ATRP-PISA), and ring-opening polymerization-mediated PISA (ROP-PISA) are discussed carefully. Afterward, recent biomedical applications of PISA are illustrated from the following aspects, i.e., bioimaging, disease treatment, biocatalysis, and antimicrobial. In the end, current achievements and future perspectives of PISA are given. It is envisioned that PISA strategy can bring great chance for future design and construction of functional nano-vehicles.

Polymerization‐induced self‐assembly for drug delivery: A critical appraisal

“…The preparation of polymeric NPs, such as micelles and polymersomes, loaded with therapeutic cargo via PISA offers several advantages, but also certain challenges when compared to conventional self-assembly methods. 43 In situ cargo encapsulation, that is, concurrent polymer synthesis, self-assembly, and cargo encapsulation (Figure 4A, left), following a seemingly straightforward one-pot procedure is one of the key advantages. The reduction of necessary experimental steps compared to conventional SA approaches may significantly simplify and speed up the production of loaded NPs.…”

“…156 Next to photoinitiation, other exogeneous initiation mechanisms have been explored for aqueous RAFT-PISA, such as redox-initiation, enzymatic initiation, and sono-RAFT (initiation via ultrasound) in which radicals are formed in situ via homolysis of water. 39 Aside from advancing RAFT protocols, PISA has been extended to other polymerization techniques, [41][42][43] most notably radical ring-opening polymerization (rROP) with cyclic ketene acetals and (aqueous) ROP of N-carboxyanhydrides (NCA-ROP). 157 These techniques allow for incorporating biodegradable groups into the polymer backbone; something not possible with the commonly applied RAFT polymerizations for PISA (Section 4.4).…”

“…39,40 However, atom transfer radical polymerization (ATRP), nitroxidemediated radical polymerization (NMP), ring-opening (metathesis) polymerization (RO(M)P), as well as more exotic techniques, such as organotellurium-mediated living radical polymerization (TERP), anionic polymerization, addition-fragmentation chain transfer (AFCT) polymerization, reversible complexation-mediated polymerization (RCMP), and cobalt-mediated radical polymerization (CMRP), have been successfully applied for PISA as well. [41][42][43] As such, PISA is compatible with a wide range of monomers, solvents, additives, and initiation mechanisms that go beyond thermal initiation, for example, photo-, redox/oscillatory reaction-, enzyme-, and ultrasound wave-initiation. 44 Given this versatility, PISA has the potential of being a synthetic workhorse for biomedical and pharmaceutical applications, such as bioimaging, [45][46][47] biocatalysis, 48 tissue culture, 49 and cell preservation.…”

“…50,51 One of the most envisioned applications of PISA is, however, the preparation of polymeric NPs for drug delivery. 43,[52][53][54][55] Incorporating therapeutic agents, such as small (hydrophobic)…”

Recent progress in polymerization‐induced self‐assembly: From the perspective of driving forces

“…[66] Furthermore, the controllable preparation of polymer assemblies with high concentration has greatly promoted the diversified applications of polymer assemblies. Besides the application in drug delivery, [67][68][69][70][71] polymer assemblies prepared by PISA have recently been exploited as artificial organelles and synthetic protocells, [72][73][74][75][76] nanoreactors, [77][78][79] Pickering emulsifiers, [80][81][82][83][84][85][86] functional gels, [81,[87][88][89] ice recrystallization inhibitors, [90,91] nano-splitters, [92] etc.…”