Carbon nanohorns have emerged as a promising platform for drug delivery due to their unique structural and physicochemical properties. These nanostructures consist of conical graphene tubules aggregated into spherical assemblies, typically 80-100 nm in diameter, with individual horn-like projections extending outward. The high surface area, ranging from 300 to 1400 m²/g depending on synthesis conditions, provides ample space for drug adsorption and functionalization. Unlike other carbon-based carriers, their closed conical structure eliminates the endotoxin risks associated with open-ended carbon nanotubes while maintaining excellent biocompatibility.

The drug loading capacity of carbon nanohorns stems from their porous architecture, which includes internal nanochannels and interstitial spaces between aggregated horns. Studies have demonstrated loading efficiencies exceeding 60% for hydrophobic chemotherapeutic agents such as doxorubicin and paclitaxel. The loading process typically occurs through physical adsorption, π-π stacking interactions, or covalent conjugation to surface-modified nanohorns. The absence of metallic catalyst residues from their production process, achieved through pure graphite vaporization, enhances their biological safety profile compared to some other carbon nanomaterials.

Surface modification strategies enable targeted drug delivery while improving aqueous dispersibility. Polyethylene glycol conjugation extends circulation time by reducing opsonization, with modified nanohorns showing blood circulation half-lives up to 20 hours in murine models. For active targeting, ligands such as folic acid, peptides, or antibodies can be attached to the nanohorn surface through carboxyl groups introduced by oxidative treatment. These modifications typically maintain the structural integrity of the nanohorns while conferring specific cellular recognition properties.

Controlled release mechanisms exploit the responsive nature of functionalized carbon nanohorns. pH-sensitive linkages enable drug release in acidic tumor microenvironments or endosomal compartments, with studies showing 70-80% payload release at pH 5.0 compared to less than 20% at physiological pH. Near-infrared light exposure can trigger release through local heating of the nanohorns, which exhibit strong optical absorption in the NIR window. This photothermal effect also provides synergistic therapy, with temperature increases of 10-15°C sufficient to enhance drug diffusion while causing localized hyperthermia.

In vivo studies have validated the therapeutic potential of carbon nanohorn-based delivery systems. Intravenous administration in tumor-bearing mice demonstrated preferential accumulation in tumor tissue via the enhanced permeability and retention effect, with tumor-to-normal tissue ratios reaching 8:1 at 24 hours post-injection. Radiolabeled tracking studies confirmed gradual clearance through hepatobiliary pathways, with less than 5% remaining in major organs after 30 days. The absence of significant inflammatory responses in these studies supports their biocompatibility.

The unique structure of carbon nanohorns allows for combination therapy approaches. Their hollow interiors can encapsulate therapeutic gases such as nitric oxide, while the outer surfaces carry chemotherapeutic drugs. This dual loading capability has shown improved efficacy in cancer models, with one study reporting 90% tumor growth inhibition compared to 60% for single-agent delivery. The gas release can be controlled by external stimuli, adding another dimension to the therapeutic regimen.

Biodistribution studies using fluorescence-labeled nanohorns reveal distinct pharmacokinetic profiles depending on surface modifications. Neutral charged nanohorns exhibit longer circulation times than their negatively or positively charged counterparts. Liver and spleen accumulation remains the primary clearance pathway, accounting for approximately 60% of administered dose within 48 hours, while renal clearance contributes minimally due to the particle size exceeding glomerular filtration thresholds.

Stability studies of drug-loaded nanohorns indicate maintained therapeutic activity after storage at 4°C for six months, with less than 10% drug leakage observed. The carbon framework provides protection against drug degradation, particularly for light-sensitive compounds. This stability advantage over liposomal or polymeric carriers enhances their translational potential.

Recent advances have explored theranostic applications by combining drug delivery with imaging capabilities. Gadolinium-loaded nanohorns serve as MRI contrast agents while simultaneously delivering chemotherapeutic payloads. The inherent Raman scattering properties of the carbon structure allow for tracking without additional labels, providing multimodal imaging potential.

Comparative studies with other nanocarriers highlight distinct advantages of carbon nanohorns. Their higher thermal stability compared to liposomes enables sterilization by autoclaving, and their mechanical strength surpasses that of polymeric nanoparticles. Unlike mesoporous silica particles, carbon nanohorns do not suffer from structural dissolution in physiological conditions, ensuring consistent drug release profiles.

Scale-up production methods have been developed to meet potential clinical demands. The laser ablation synthesis technique yields gram quantities per hour with batch-to-batch consistency in size and morphology. This scalability addresses a critical challenge in translating nanomaterial-based therapies to clinical applications.

Ongoing research focuses on optimizing the balance between drug loading and dispersibility, as excessive functionalization can reduce the available surface area for drug adsorption. Advanced characterization techniques, including in situ TEM observation of drug release, provide insights into structure-function relationships that guide these optimization efforts.

The combination of high payload capacity, controlled release characteristics, and biocompatibility positions carbon nanohorns as a versatile platform for next-generation drug delivery systems. Their unique structural features address several limitations of existing nanocarriers while offering additional therapeutic modalities through their intrinsic physical properties. Continued development of targeted formulations and combination therapies will further expand their potential in precision medicine applications.