Employing theranostic nanoparticles, which combine both therapeutic and diagnostic capabilities in one dose, has promise to propel the biomedical field toward personalized medicine. This review ...presents an overview of different theranostic strategies developed for the diagnosis and treatment of disease, with an emphasis on cancer. Herein, therapeutic strategies such as nucleic acid delivery, chemotherapy, hyperthermia (photothermal ablation), photodynamic, and radiation therapy are combined with one or more imaging functionalities for both in vitro and in vivo studies. Different imaging probes, such as MRI contrast agents (T1 and T2 agents), fluorescent markers (organic dyes and inorganic quantum dots), and nuclear imaging agents (PET/SPECT agents), can be decorated onto therapeutic agents or therapeutic delivery vehicles in order to facilitate their imaging and, in so doing, gain information about the trafficking pathway, kinetics of delivery, and therapeutic efficacy; several such strategies are outlined. The creative approaches being developed for these classes of therapies and imaging modalities are discussed, and the recent developments in this field along with examples of technologies that hold promise for the future of cancer medicine are highlighted.
3D printing is an essential tool for rapid prototyping in a variety of sectors such as automotive and public health. The 3D printing market is booming, and it is projected that it will continue to ...thrive in the coming years. Unfortunately, this rapid growth has led to an alarming increase in the amount of 3D printed plastic waste. 3D printing processes such as stereolithography (SLA) and digital light projection (DLP) in particular generally produce petroleum-based thermosets that are further worsening the plastic pollution problem. To mitigate this 3D printed plastic waste, sustainable alternatives to current 3D printing materials must be developed. The present review provides a comprehensive overview of the sustainable advances in SLA/DLP 3D printing to date and offers a perspective on future directions to improve sustainability in this field. The entire life cycle of 3D printed parts has been assessed by considering the feedstock selection and the end-of-use of the material. The feedstock selection section details how renewable feedstocks (from lignocellulosic biomass, oils, and animal products) or waste feedstocks (
e.g.
, waste cooking oil) have been used to develop SLA/DLP resins. The end-of-use section describes how materials can be reprocessed (
e.g.
thermoplastic materials or covalent adaptable networks) or degraded (through enzymatic or acid/base hydrolysis of sensitive linkages) after end-of-use. In addition, studies that have employed green chemistry principles in their resin synthesis and/or have shown their sustainable 3D printed parts to have mechanical properties comparable to commercial materials have been highlighted. This review also investigates how aspects of sustainability such as recycling for feedstock/end-of-use or biodegradation of 3D printed parts in natural environments can be incorporated as future research directions in SLA/DLP.
The 3D printing market is booming in various sectors coupled with an alarming increase in 3D printed plastic waste. This review summarizes sustainable advances in SLA/DLP plastic 3D printing to date and offers a perspective for further developments.
Responsive polymers with properties designed to interact with their surrounding environment are enabling “smart” design features for custom biomaterials. Numerous applications are being innovated, ...ranging from diagnostics and imaging to tissue engineering and drug delivery. Herein, I feature a collection of research articles published in ACS Macro Letters that highlight an array of innovative chemical attributes such as pH-triggered hydrolytic degradation, reduction-based release, photomodulation, glucose responsiveness, thermal sensitivity, and membrane permeating peptides. The chemical, physical, mechanical, and morphological properties of polymeric structures can be custom tailored to enhance numerous features such as biological delivery, pharmaceutical potency and safety, disease diagnosis, and antigen/biomaker detection.
The advent of genome editing has transformed the therapeutic landscape for several debilitating diseases, and the clinical outlook for gene therapeutics has never been more promising. The therapeutic ...potential of nucleic acids has been limited by a reliance on engineered viral vectors for delivery. Chemically defined polymers can remediate technological, regulatory, and clinical challenges associated with viral modes of gene delivery. Because of their scalability, versatility, and exquisite tunability, polymers are ideal biomaterial platforms for delivering nucleic acid payloads efficiently while minimizing immune response and cellular toxicity. While polymeric gene delivery has progressed significantly in the past four decades, clinical translation of polymeric vehicles faces several formidable challenges. The aim of our Account is to illustrate diverse concepts in designing polymeric vectors towards meeting therapeutic goals of in vivo and ex vivo gene therapy. Here, we highlight several classes of polymers employed in gene delivery and summarize the recent work on understanding the contributions of chemical and architectural design parameters. We touch upon characterization methods used to visualize and understand events transpiring at the interfaces between polymer, nucleic acids, and the physiological environment. We conclude that interdisciplinary approaches and methodologies motivated by fundamental questions are key to designing high-performing polymeric vehicles for gene therapy.
Chemically defined vectors such as cationic polymers are versatile alternatives to engineered viruses for the delivery of genome-editing payloads. However, their clinical translation hinges on ...rapidly exploring vast chemical design spaces and deriving structure–function relationships governing delivery performance. Here, we discovered a polymer for efficient intracellular ribonucleoprotein (RNP) delivery through combinatorial polymer design and parallelized experimental workflows. A chemically diverse library of 43 statistical copolymers was synthesized via combinatorial RAFT polymerization, realizing systematic variations in physicochemical properties. We selected cationic monomers that varied in their pK a values (8.1–9.2), steric bulk, and lipophilicity of their alkyl substituents. Co-monomers of varying hydrophilicity were also incorporated, enabling elucidation of the roles of protonation equilibria and hydrophobic–hydrophilic balance in vehicular properties and performance. We screened our multiparametric vector library through image cytometry and rapidly uncovered a hit polymer (P38), which outperforms state-of-the-art commercial transfection reagents, achieving nearly 60% editing efficiency via nonhomologous end-joining. Structure–function correlations underlying editing efficiency, cellular toxicity, and RNP uptake were probed through machine learning approaches to uncover the physicochemical basis of P38’s performance. Although cellular toxicity and RNP uptake were solely determined by polyplex size distribution and protonation degree, respectively, these two polyplex design parameters were found to be inconsequential for enhancing editing efficiency. Instead, polymer hydrophobicity and the Hill coefficient, a parameter describing cooperativity-enhanced polymer deprotonation, were identified as the critical determinants of editing efficiency. Combinatorial synthesis and high-throughput characterization methodologies coupled with data science approaches enabled the rapid discovery of a polymeric vehicle that would have otherwise remained inaccessible to chemical intuition. The statistically derived design rules elucidated herein will guide the synthesis and optimization of future polymer libraries tailored for therapeutic applications of RNP-based genome editing.
Polymer composition and morphology can affect the way polymers interact with biomolecules, cell membranes, and intracellular components. Herein, diblock, triblock, and statistical polymers that ...varied in charge center type (primary and/or tertiary amines) were synthesized to elucidate the role of polymer composition on plasmid DNA complexation, delivery, and cellular toxicity of the resultant polyplexes. The polymers were synthesized via RAFT polymerization and were composed of a carbohydrate moiety, 2-deoxy-2-methacrylamido glucopyranose (MAG), a primary amine group, N-(2-aminoethyl) methacrylamide (AEMA), and/or a tertiary amine moiety, N,N -(2-dimethylamino)ethyl methacrylamide (DMAEMA). The lengths of both the carbohydrate and cationic blocks were kept constant while the primary amine to tertiary amine ratio was varied within the polymers. The polymers were characterized via nuclear magnetic resonance (NMR) and size exclusion chromatography (SEC), and the polyplex formulations with pDNA were characterized in various media using dynamic light scattering (DLS). Polyplexes formed with the block copolymers were found to be more colloidally stable than statistical copolymers with similar composition, which rapidly aggregated to micrometer sized particles. Also, polymers composed of a higher primary amine content were more colloidally stable than polymers consisting of the tertiary amine charge centers. Plasmid DNA internalization, transgene expression, and toxicity were examined with each polymer. As the amount of tertiary amine in the triblock copolymers increased, both gene expression and toxicity were found to increase. Moreover, it was found that increasing the content of tertiary amines imparted higher membrane disruption/destabilization. While both block and statistical copolymers had high transfection efficiencies, some of the statistical systems exhibited both higher transfection and toxicity than the analogous block polymers, potentially due to the lack of a hydrophilic block to screen membrane interaction/disruption. Overall, the triblock terpolymers offer an attractive composition profile that exhibited interesting properties as pDNA delivery vehicles.
Epoxy resins are ubiquitous in high-performance composite applications because of their excellent mechanical strength, thermal and chemical resistance, strong adhesion, and low shrinkage after ...curing. Bio-based epoxy resins derived from natural products such as carbohydrates offer tremendous potential for creating new polymeric materials. Sugars and their derivatives often offer great biodegradability and functionality such as the presence of multiple hydroxyl groups that impart highly cross-linked polymer networks. Moreover, their ring structures can afford polymers with high glass transition temperatures. To develop epoxy resins containing sustainably sourced feedstocks, we designed and synthesized trehalose- and β-cyclodextrin-based carboxylic acid hardeners for epoxy resins and examined the thermal, mechanical, and adhesive properties of the resulting materials. Trehalose and β-cyclodextrin were succinylated with excess succinic anhydride, and the resulting carboxylic acid hardeners formed homogeneous mixtures with trimethylolpropane triglycidyl ether (TTE) in different carboxyl–epoxide ratios. The cured resins were found to be thermally stable (T d5 > 300 °C) and display high Young’s moduli of up to 1.4 and 1.8 GPa with mechanical strengths of 47 and 64 MPa for the trehalose- and β-cyclodextrin-based epoxy resins, respectively. Preliminary adhesion tests showed that the cured resins exhibit excellent lap-shear strengths of 3600 and 2100 psi, respectively. The resins were also degradable into water-soluble components in both aqueous acidic and basic solutions but were relatively stable from hydrolysis in neutral aqueous conditions. These results imply that this novel class of hardeners are promising feedstocks for renewable high performance epoxy resins.
Photocured polymers have recently gained tremendous interest for a wide range of applications, such as industrial prototyping/additive manufacturing, electronics, medical/dental devices, and tissue ...engineering. However, current development of photoinitiated thermosetting formulations is mostly centered on commercial monomers/oligomers that are petroleum-derived and not environmentally friendly. This work aims to develop natural phenolic-based (meth)acrylates to expand the use of sustainable and mechanically robust 3D printable formulations. Utilizing thiol–ene chemistry, bifunctional 3,6-dioxa-1,8-octanedithiol eugenol acrylate ( E ) was synthesized through a highly efficient, scalable method. Real-time infrared spectra and photorheology studies revealed that E exhibits rapid photocuring kinetics and that the viscosity, glass transition temperature ( T g ) and thermal properties of this material can be tuned by adding a sustainable reactive diluent, guaiacyl methacrylate ( G ). The effect of adding a crosslinker to binary GE monomers was further investigated by incorporating vanillyl alcohol dimethacrylate ( V ) or trimethylolpropane trimethacrylate ( T ). At 20 mol%, V showed a moderate improvement in curing rate and a lower degree of cross-linking than T due to the bifunctionality of V . However, the aromaticity of V provided more resistance to chain deformation and breakage within the network, demonstrating storage moduli and tensile strengths up to 3.4 GPa and 62 MPa, respectively. The distinct impact of the crosslinkers on the tensile behaviors of glassy terpolymers was correlated to the cohesive energy density. Ternary formulations GEV 60–20–20 by mol% with 2 wt% TPO photoinitiator were successfully printed using a commercial desktop stereolithographic 3D printer with 405 nm violet laser source. This work demonstrates a versatile, sustainable, and scalable synthetic strategy to design a class of natural phenolic acrylates for sustainable photocured formulations with potential translation to high performance 3D printing.
ABA triblock copolymers are used as thermoplastic elastomers (TPEs) for a wide variety of applications. Herein, we describe incorporation of sugar-based glassy components to create sustainable ...triblock copolymers as alternatives for commodity TPEs. Poly(glucose-6-acrylate-1,2,3,4-tetraacetate) PGATA and poly(acetylated acrylic isosorbide) PAAI end blocks were chain-extended from a poly(n-butyl acrylate) PnBA midblock. PAAI–PnBA–PAAI exhibited excellent adhesion properties: peel = 8.74 N cm–1, loop tack = 2.96 N cm–2, no shear failure up to 100 h, and shear adhesion failure temperature (SAFT) = 60 °C. Although similar peel adhesion and higher loop tack were observed for PGATA–PnBA–PGATA, the shear strength and SAFT were moderate (18 h and 42 °C, respectively). PAAI–PnBA–PAAI are tough elastomers and demonstrated high stress and elongation at break (σ = 6.5 MPa and ε = 620%, respectively) while the GATA-based analogue exhibited weaker tensile properties (σ = 0.8 MPa and ε = 476%). To address this, the anomeric hydroxyl groups of GATA units were selectively deprotected to promote self-complementary hydrogen bonding in the glassy domains, resulting in 80% enhancement in the ultimate tensile stress at break (σ = 1.5 MPa). This study aims to demonstrate effects of noncovalent interactions, such as chain entanglements and self-complementary hydrogen bonding, to enhance the adhesion and mechanical performance of sugar-derived TPEs.
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