This study represents a successful approach toward employing polycaprolactone–polyamidoamine (PCL–PAMAM) linear dendritic block copolymer (LDBC) nanoparticles as small-molecule carriers in NIR imaging and photothermal therapy. A feasible and robust synthetic strategy was used to synthesize a library of amphiphilic LDBCs with well-controlled hydrophobic-to-hydrophilic weight ratios. Systems with a hydrophobic weight ratio higher than 70% formed nanoparticles in aqueous media, which show hydrodynamic diameters of 51.6 and 96.4 nm. These nanoparticles exhibited loading efficiencies up to 21% for a hydrophobic molecule and 64% for a hydrophilic molecule. Furthermore, successful cellular uptake was observed via trafficking into endosomal and lysosomal compartments with an encapsulated NIR theranostic agent (C3) without inducing cell death. A preliminary photothermal assessment resulted in cell death after treating the cells with encapsulated C3 and exposing them to NIR light. The results of this work confirm the potential of these polymeric materials as promising candidates in theranostic nanomedicine.

Herein, we present a facile and comprehensive synthetic methodology for the preparation of polyester‐polyamidoamine (PAMAM) (i.e., polyester: polylactide [PLA] (hydrophobic) and polyamidoamine, PAMAM [hydrophilic]) polymers. A library of PLA‐PAMAM linear dendritic block copolymers (LDBCs) in which both l and d, l polylactide were employed in mass ratios of 30:70, 50:50, 70:30, and 90:10 (PLA:PAMAM) were synthesized and analyzed. When placed in aqueous media, the immiscibility of the hydrophilic and hydrophobic segments leads to nanophase‐segregation exhibited as the formation of aggregates (e.g., vesicles, worms, and/or micelles). By employing both stereochemical configurations of PLA, the differentiation in mass ratios of PLA‐PAMAM aided in elucidating the structure–property relationships of the LDBC system and provided a means toward the control of nanoparticle morphology. Transmission electron microscopy and dynamic light scattering afford the size and shape of the nanoparticles with diameters ranging from 10.6 for low mass ratios to 122.4 nm for high mass ratios of PLA‐PAMAM and positive zeta‐potential values between +24.7 mV and +48.2 mV. Furthermore, small‐angle X‐ray scattering (SAXS) studies were employed to obtain more detailed information on the morphological assemblies constructed via direct dissolution. Such insights provide a pathway toward nanomaterials with unique morphologies and tunable properties deemed relevant in the development of next generation biomaterials. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1448–1459

Ionic liquid-functionalized linear-dendritic block copolymer nanoparticles show facile assemblies and red blood cell hitchhiking in whole blood.

Shortwave infrared (SWIR)-emitting small molecules are desirable for biological imaging applications. In this study, four novel pentamethine indolizine cyanine dyes were synthesized with N,N-dimethylaniline-based substituents on the indolizine periphery at varied substitution sites. The dyes are studied via computational chemistry and optical spectroscopy both in solution and when encapsulated. Dramatic spectral shifts in the absorption and emission spectrum wavelengths with added donor groups are observed. Significant absorption and emission with an emissive quantum yield as high as 3.6% in the SWIR region is possible through the addition of multiple donor groups per indolizine.

This study summarizes the synthesis, characterization, and evaluation of a library of biocompatible selfassembling Janus dendrimers (JDs) and their resulting nanostructures possessing either a cationic (NH 3 +), anionic (COO À), or neutral (OH) surface. Strategically designed for applications in therapeutic delivery, the dendrimers are comprised of a polyamidoamine (PAMAM) dendron as the hydrophilic portion and fatty acid (FA) functionalized dendrons as the hydrophobic portion. The physicochemical characterization and in vitro cell viability of amphiphilic JDs were performed. Microscopy (TEM) and dynamic light scattering (DLS) analysis indicate the size (i. e., diameters) of spherical nanoaggregates ranging from 40 to 100 nm with zeta-potential values ranging from À 17.9 to + 58.7 mV with respect to the terminal functional group of the JD employed. Furthermore, these systems exhibited spherical nanoaggregates with critical aggregate concentrations (CAC) ranging from 2.8 to 7.0 mg/L. At low concentrations (< 200 μg/mL), JDs nanoaggregates showed minimal cell growth inhibitory properties in the in vitro testing, demonstrating their safety. The results of this study prove that a simple yet strategic combination of chemically distinctive dendritic segments can afford a versatile library of unique JDs nanoplatforms with excellent potential for biomedical applications.

This study represents a comparative analysis of the solution behavior and self-assembly pattern of two linear dendritic block copolymers (LDBCs) composed of a generation 3 polyamidoamine (PAMAM) dendron as the dendritic block and poly(caprolactone) (PCL) as the linear block, the latter of which is modified with pendant phenyl groups. Phenyl substituents were introduced to induce physical cross-linking in LDBC nanoparticles via π−π stacking. A synthetic strategy was developed to access phenyl substituted LDBCs through an ε-caprolactone monomer derivative followed by ring-opening polymerization to form a library of LDBCs with yields above 83%. Polymersome-like nanoparticles were observed in water with a 74.4 nm average diameter. Cross-linked LDBC nanoparticles demonstrated a 37.1% relative decrease in the critical aggregation concentration (CAC) and a 27.3−41.2% relative increase of hydrophobic loading efficiency relative to unsubstituted LDBCs. Nanoparticles loaded with a potential photothermal agent (phenyl indolizine-C5 (C5)) showed a photothermal efficiency of 49.4% with a heating temperature of 44.4 °C. These nanoparticles were efficiently loaded into HEK293 cells with cell viability above 87.5% at the highest concentration. Upon illumination with red light, nanoparticles loaded with photothermal agent were able to induce cell death in cancer cells. This work suggests that the phenyl substituted LDBCs form nanoparticles with enhanced stability and loading efficiencies compared to conventional nonphenylated systems and display a greater potential to be used as nanocarriers in theranostic nanomedicine.

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The challenges faced with current fluorescence imaging agents have motivated us to study two nanostructures based on a hydrophobic dye, 6H-pyrrolo[3,2-b:4,5-b’]bis [1,4]benzothiazine (TRPZ). TRPZ is a heteroacene with a rigid, pi-conjugated structure, multiple reactive sites, and unique spectroscopic properties. Here we coupled TRPZ to a tert-butyl carbamate (BOC) protected 2,2-bis(hydroxymethyl)propanoic acid (bisMPA) dendron via azide-alkyne Huisgen cycloaddition. Deprotection of the protected amine groups on the dendron afforded a cationic terminated amphiphile, TRPZ-bisMPA. TRPZ-bisMPA was nanoprecipitated into water to obtain nanoparticles (NPs) with a hydrodynamic radius that was &lt;150 nm. For comparison, TRPZ-PG was encapsulated in pluronic-F127 (Mw = 12 kD), a polymer surfactant to afford NPs almost twice as large as those formed by TRPZ-bisMPA. Size and stability studies confirm the suitability of the TRPZ-bisMPA NPs for biomedical applications. The photophysical properties of the TRPZ-bisMPA NPs show a quantum yield of 49%, a Stokes shift of 201 nm (0.72 eV) and a lifetime of 6.3 ns in water. Further evidence was provided by cell viability and cellular uptake studies confirming the low cytotoxicity of TRPZ-bisMPA NPs and their potential in bioimaging.