Recent Advances in Drug Release, Sensing, and Cellular Uptake of Ring-Opening Metathesis Polymerization (ROMP) Derived Poly(olefins)

Abstract

The synthesis and applications of ring-opening metathesis polymerization (ROMP) derived poly(olefins) have emerged as an exciting area of great interest in the field of biomaterials science. The major focus of this mini-review is to present recent advances in the synthesis of functional materials using ROMP-derived poly(olefins) utilized for drug release, sensing, and cellular uptake in the past seven years (2015-2022). This review reveals that materials synthesized by ROMP-derived well-defined functional poly(olefins) stand to be highly promising systems for medical as well as biological studies. Thus, this review may prove to be beneficial for the design and development of new smart and flexible-functionality ROMP-based polymeric materials for various biological applications.

Figure 1

(a) Representative Mo- or W-based Schrock-type and Ru-based Grubbs- or Hoveyda–Grubbs-type alkylidene complexes and (b) various mono- and bicycloalkene monomers.

Scheme 1. General Schematic Representation of the ROMP of Fluorophore-Incorporated Cycloolefins: (a) Homopolymerization; (b) Copolymerization

Figure 2

Enzyme-responsive and paclitaxel-conjugated diblock copolymer P1, self-assembled into polymer nanoparticles, and subsequent morphology change in response to MMP. Reprinted with permission from ref (9). Copyright 2015, John Wiley and Sons, Inc.

Figure 3

(a) Maximum tolerated dose (MTD) of IV injection, (b) tumor growth IT injection, and (c) tumor growth IV injection. Reprinted with permission from ref (9). Copyright 2015, John Wiley and Sons, Inc.

Figure 4

(a) Immune-therapeutics-loaded copolymer P2 self-assembled into micelles and (b) morphological studies by TEM and SIM analysis. Reprinted with permission from ref (10). Copyright 2019, John Wiley and Sons, Inc.

Figure 5

Self-assembled linear-brush polymer P3 and cis-platinum-loaded acid degradable cross-linked polymer P4 for the generation of acid-degradable cross-linked vesicles.

Figure 6

Pt(II)-loaded amphiphilic copolymer P5 self-assembled nanoparticles. Reprinted with permission from ref (13). Copyright 2018, American Chemical Society.

Figure 7

Efficacy of P5 with whole-animal and ex vivo organ targeting data. (a, top left) Comparison of l-Pep-Pt-NP to d-Pep-Pt-NP and oxaliplatin with respect to Pt and saline following IT injection. (a, top right) Time course of live-animal fluorescence imaging following IT injection of l-Pep-Pt-NP ex vivo tissue analysis as well as fluorescence imaging of tumor, liver, spleen, and kidney. (b) SIM imaging analysis. Reprinted with permission from ref (13). Copyright 2018, American Chemical Society.

Figure 8

Structure of the amphiphilic copolymer P6.

Figure 9

Polymer structure of P7.

Figure 10

(top left) Structure of ROMP-derived polymer P8. (top right) Image representing the green-light-triggered CO release from polymer P8. (a, bottom left) Changes in the absorption spectra of P8 under light irradiation. Inset: fluorescence intensity in the emission spectrum at λ = 532 nm following exposure to light vs time intervals. (b, bottom right) Amount of CO release from P8. Reprinted with permission from ref (16). Copyright 2019, American Chemical Society.

Scheme 2. Schematic Representation of a Chemosensor-Appended Polymer Backbone

Scheme 3. Possible Binding Modes of P9 with Metal Ions

Scheme 4. Selective Extraction of Cu²⁺ Ion by Polymer P10

Scheme 5. (Top Left) Possible Binding Mechanisms of P11 with Al³⁺ Ions, (Top Right) Specific Labeling of P11 in Lysosomes, and Changes in (a) Absorption and (b) Emission Spectra of P11 in the Absence and the Presence of Different Metal Ions

Mⁿ⁺ = Na⁺, K⁺, Mg²⁺, Ca²⁺, Ba²⁺, Cu²⁺, Ni²⁺, Zn²⁺, Cd²⁺, Co²⁺, Fe²⁺, Cr³⁺, Pb²⁺, Al³⁺, and Hg²⁺ in aqueous HEPES buffer–acetonitrile medium. Reprinted with permission from ref (21). Copyright 2020, Springer Nature.

Scheme 6. Polymer P12 for the Synthesis of Nanoparticles

Scheme 7. Proposed Noncovalent Interaction Mode between P13 and P14 with Dopamine HCl

Figure 11

(a) Structure of ROMP-derived homopolymers P15 and P16. (b) Confocal fluorescence images of HeLa cells incubated with P15 (A1–A3 and B1–B3). Reprinted with permission from ref (24). Copyright 2016, Wiley-VCH.

Scheme 8. (a) Sensing Behavior of P17 and P18 in the Presence of Dichloroethyl Phosphate (DCP) and (b) Molecular Structures of P19 and P20, Respectively, for Di- and Triblock Copolymers

Figure 12

Grafting CWA-responsive copolymers P21 and P22 from nanoparticle-norbornene as well as CNT-norbornene via ROMP.

Scheme 9. Formulation of the High Internal Phase Emulsions (HIPEs) and Schematic Representation of the Structure of P23

Figure 13

Cellular internalization of GSGSG-incorporated copolymer P24 and KLA peptide based homopolymer P25.

Figure 14

(a) Flow cytometry data displaying fluorescent signatures of HeLa cells treated with the polymers (m ≈ 60) and their monomeric counterparts. The R control is a block copolymer that contains a single Arg attached via a short linker to each polymer side chain of this first polymer block. “Flu” is the fluorescein end label present in P24. (b) Live-cell confocal microscopy images showing the average intensities from six consecutive 1 μm slices of HeLa cells treated with peptides and polymers (m ≈ 60). Reprinted with permission from ref (33). Copyright 2016, Royal Society of Chemistry.

Figure 15

Peptide conjugated copolymer structure P26 (conjugation to the N-terminus or ε-amino group of a C-terminal lysine residue of the peptide). Reprinted with permission from ref (34). Copyright 2017, American Chemical Society.