Amphiphilic block copolymer micelles have emerged as versatile nanocarriers in theranostic applications, combining therapeutic and diagnostic functions within a single platform. These micelles self-assemble in aqueous solutions, with hydrophobic blocks forming the core to encapsulate drugs and imaging agents, while hydrophilic blocks form the protective corona. The critical micelle concentration (CMC) is a fundamental parameter determining micelle stability, typically ranging from 0.1 to 10 mg/L for common copolymers like polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA). Below the CMC, micelles disintegrate into unimers, releasing their payload prematurely. High CMC values indicate lower stability, necessitating careful polymer selection to balance structural integrity and drug-loading efficiency.

Stimuli-responsive micelles enhance controlled release by disintegrating in response to specific triggers. pH-sensitive micelles exploit the acidic tumor microenvironment (pH 6.5–6.8) or endosomal compartments (pH 5.0–5.5). For example, poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) undergoes protonation in acidic conditions, destabilizing the micelle core. Redox-responsive systems leverage the high glutathione concentration in cancer cells (2–10 mM vs. 2–20 μM extracellularly). Disulfide bonds in the copolymer backbone cleave under reducing conditions, enabling intracellular drug release. Dual-responsive systems combining pH and redox triggers further improve specificity and reduce off-target effects.

Imaging probes like superparamagnetic iron oxide nanoparticles (SPIONs) and fluorescent dyes integrate seamlessly into micelle cores or coronas. SPIONs enable magnetic resonance imaging (MRI) due to their strong T2 contrast effects, while near-infrared dyes like indocyanine green permit real-time tracking. Co-encapsulation of drugs and imaging agents requires optimization to prevent fluorescence quenching or magnetic interference. Payload capacity depends on core hydrophobicity and compatibility, with typical drug-loading contents of 5–20 wt%. Excessive loading can destabilize micelles, reducing circulation time and promoting aggregation.

Genexol-PM, a clinically approved PEG-PLGA micelle loaded with paclitaxel, demonstrates the translational potential of this technology. It exhibits a 3-fold higher maximum tolerated dose (390 mg/m²) compared to conventional paclitaxel formulations, attributed to reduced Cremophor EL toxicity. The micellar structure enhances tumor accumulation via the enhanced permeability and retention (EPR) effect, though heterogeneity in tumor vasculature limits uniform distribution. Clinical trials show response rates of 37–58% in metastatic breast cancer, underscoring the therapeutic benefit.

Trade-offs between stability and payload capacity remain a key challenge. Increasing hydrophobic block length enhances core stability but may reduce CMC to impractical levels. Conversely, shorter hydrophobic segments improve drug loading but risk premature disintegration. Crosslinking the core or corona can stabilize micelles without compromising responsiveness, though excessive crosslinking may hinder drug release. Alternative strategies include blending copolymers or introducing auxiliary agents like cholesterol to modulate micelle properties.

Future directions focus on multifunctional designs incorporating targeting ligands (e.g., folate, peptides) to improve specificity. However, ligand density must be optimized to avoid opsonization and rapid clearance by the reticuloendothelial system. Advances in polymerization techniques, such as living radical polymerization, enable precise control over block lengths and architectures, facilitating tailored micelle formulations. Despite these innovations, scalability and reproducibility in manufacturing remain hurdles for clinical translation.

In summary, amphiphilic block copolymer micelles represent a promising theranostic platform, with stimuli-responsive features enabling spatiotemporal control over drug delivery and imaging. Clinical successes like Genexol-PM validate their potential, though optimizing the balance between stability, payload capacity, and responsiveness is critical for broader adoption. Continued refinement of polymer chemistry and formulation strategies will expand their utility in precision medicine.