Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

/pdf/degradable-controlled-release-polymers-and-polymeric-1y322ha58z.pdf

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer–drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving...

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies.

Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.

/pdf/controlled-drug-delivery-vehicles-for-cancer-treatment-and-1osv5b96qe.pdf

Controlled drug delivery vehicles for cancer treatment and their performance.

New achievements in the realm of nanoscience and innovative techniques of nanomedicine have moved micro/nanoparticles (MNPs) to the point of becoming actually useful for practical applications in the near future. Various differences between the extracellular and intracellular environments of cancerous and normal cells and the particular characteristics of tumors such as physicochemical properties, neovasculature, elasticity, surface electrical charge, and pH have motivated the design and fabrication of inventive “smart” MNPs for stimulus-responsive controlled drug release. These novel MNPs can be tailored to be responsive to pH variations, redox potential, enzymatic activation, thermal gradients, magnetic fields, light, and ultrasound (US), or can even be responsive to dual or multi-combinations of different stimuli. This unparalleled capability has increased their importance as site-specific controlled drug delivery systems (DDSs) and has encouraged their rapid development in recent years. An in-depth understanding of the underlying mechanisms of these DDS approaches is expected to further contribute to this groundbreaking field of nanomedicine. Smart nanocarriers in the form of MNPs that can be triggered by internal or external stimulus are summarized and discussed in the present review, including pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles (NPs), mechanical- or electrical-responsive MNPs, light or ultrasound-sensitive particles, and multi-responsive MNPs including dual stimuli-sensitive nanosheets of graphene. This review highlights the recent advances of smart MNPs categorized according to their activation stimulus (physical, chemical, or biological) and looks forward to future pharmaceutical applications.

/pdf/smart-micro-nanoparticles-in-stimulus-responsive-drug-gene-1duzknz8dr.pdf

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug–drug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir–Cb conjugate self-assembles into nanoparticles in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir–Cb ADDC nanoparticles is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular inter...

Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug-drug conjugate for cancer therapy.

Hyperbranched polymers (HBPs), an important subclass of dendritic macromolecules, are highly branched, three-dimensional globular nanopolymeric architectures. Attractive features like highly branched topological structures, adequate spatial cavities, numerous terminal functional groups and convenient synthetic procedures distinguish them from the available polymers (the linear, branched, and crosslinking polymers). Due to their unique physical/chemical properties, applications of HBPs have been explored in a large variety of fields. In particular, HBPs exhibit unique advantages in the biological and biomedical systems and devices. Firstly, the way to prepare HBPs usually only involves simple one-pot reactions and avoids the complicated synthesis and purification procedures, which makes the manufacturing process more convenient, thus reducing production costs. Secondly, the large number of end-groups of HBPs provides a platform for conjugation of the functional moieties and can also be employed to tailor-make the properties of HBPs, enhancing their versatility in biological applications. Thirdly, HBPs possess excellent biocompatibility and biodegradability, controlled responsive nature, and ability to incorporate a multiple array of guest molecules through covalent or noncovalent approaches. All of these features of HBPs are of great significance for designing and producing biomaterials. To date, significant progress has been made for the HBPs in solving some of the fundamental and technical questions toward their bioapplications. The present review highlights the contribution of HBPs to biological and biomedical fields with intent to aid the researchers in exploring HBPs for bioapplications.

Dali Wang

Papers

Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug-drug conjugate for cancer therapy.

Bioapplications of hyperbranched polymers

Synthesis and applications of stimuli-responsive hyperbranched polymers

Supramolecular Copolymer Micelles Based on the Complementary Multiple Hydrogen Bonds of Nucleobases for Drug Delivery

Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging