Challenges and Opportunities of Nanomedicine: Novel Comprehensive Approaches for Brain Metastasis

Abstract

Brain metastasis is the leading cause of death in most cancer patients; thus, anti‐brain metastasis is a crucial step in cancer treatment. The unique microenvironment and pathophysiological characteristics of brain metastases hamper the development of effective treatment methods, while the advances in nanomedicine demonstrate its immense potential for addressing this challenge. In recent years, due to breakthroughs in nanotechnology, functional and complex nanomedicine is prepared and it has been extensively explored to improve the treatment of brain metastasis. Compared to traditional treatment methods, nanomedicine can combine multiple traditional treatment methods into one single medicinal format and target unique characteristics of brain metastases to enhance the treatment efficacy. This review summarizes the main obstacles in the field of brain metastasis treatment and clinical/preclinical studies and surveys the use of a variety of nanomedicine candidates as antibrain metastasis strategies for different types of brain metastases.

Single Molecular Nanomedicines Based on Macrocyclic Carrier-Drug Conjugates for Concentration-Independent Encapsulation and Precise Activation of Drugs

“…Traditional medicines act as a double-edged sword, offering potent therapeutic effects while often resulting in multiple undesirable side effects. − In the pursuit of augmenting therapeutic potential and mitigating adverse effects, researchers have developed various strategies, broadly categorized into two paradigms: one involves partial covalent modification of drugs, known as prodrugs; − the other entails noncovalent encapsulation of drugs to form nanomedicines, such as using liposomes, polymers, dendrimers, and other nanocarriers for drug delivery. − Rationally designed prodrugs or nanomedicines can to some extent enhance the drug’s solubility, stability, bioavailability, targeting, and reduce toxicity. − Additionally, they each have distinct advantages and disadvantages. Prodrugs possess clear structures and a single composition, thus exhibiting ease of production and good reproducibility, which is advantageous for clinical translation. − However, covalent modification only protects specific regions of drug molecules, often proving less effective in improving stability and reducing drug toxicity. , In contrast, nanomedicines formed through noncovalent interactions fully encapsulate and shield drug molecules. − Nevertheless, any nanomedicines based on noncovalent assemblies are inherently concentration-sensitive, potentially causing premature drug release during in vivo circulation, leading to nonspecific activation or introducing uncertainties in structure and complexity in pharmacokinetics upon assembly dissociation. − This multicomponent or multidispersed nature imposes significant limitations on the clinical translation of self-assembled nanomedicines. , Therefore, developing a novel strategy for targeted controlled drug release with explicit structure and simple composition while ensuring effective shielding of drug molecules in vivo and intrinsic concentration-independent properties holds important practical significance.…”