Anesthesia for Posterior Tracheopexy in Pediatric Patients.

Tracheobronchomalacia refers to an abnormally excessive collapse of the trachea and/or bronchi during exhalation. In the pediatric population, tracheobronchomalacia is increasingly recognized as a cause of morbidity and mortality. Historically, options for medical management and surgical intervention were limited, and patient outcomes were poor. Over the last decade, select US pediatric institutions have devoted significant resources to the establishment of dedicated surgery and anesthesia teams and the development of novel techniques for the successful identification, assessment, and surgical correction of tracheobronchomalacia in a highly complex subset of the pediatric population. The close communication, collaboration, and evolution of anesthesia techniques to meet the unique requirements of new surgical procedures have greatly improved patient safety and optimized outcomes. More than 800 cases have been performed across 2 US pediatric institutions using these techniques. This article reviews the posterior tracheopexy procedure, a newer but increasingly common surgery designed to address tracheobronchomalacia, and provides an overview of related anesthesia considerations and unique challenges. In addition, this article describes novel anesthesia techniques developed specifically to facilitate optimal diagnosis of tracheobronchomalacia and intraoperative management of posterior tracheopexy and similar airway surgeries. These include methods to safely enable 3-phase rigid dynamic bronchoscopy for accurate tracheobronchomalacia diagnosis, recurrent laryngeal nerve monitoring during cervical and thoracic surgical dissection, continuous intraoperative bronchoscopy to enable real-time images during airway reconstruction, and intraoperative assessment of airway repair adequacy to ensure successful correction of tracheobronchomalacia.

Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation.

OBJECTIVE: To validate a novel biomarker, airway impedance for extraesophageal disease. STUDY DESIGN: We prospectively recruited patients with respiratory symptoms undergoing combined endoscopy and direct laryngoscopy for the evaluation of symptoms. The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and an impedance catheter was placed onto the posterior larynx to obtain measurements. Following this, an endoscopy was performed and impedance measurements and biopsies were taken at 3 esophageal heights. Impedance values were compared within and between patients. RESULTS: Eighty-eight patients were recruited, of which 73 had complete airway and endoscopic exams. There was no significant correlation between airway impedance values and mean reflux finding scores (r2 = 0.45, P = .07). There was no significant positive correlation between airway impedance and esophageal impedance values (r2 = 0.097-0.138, P > .2). Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06). Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008). Inhaled steroids did not impact airway impedance levels (P = .7). CONCLUSIONS: Airway impedance may be an important diagnostic tool to diagnose gastroesophageal reflux or aspiration, eliminating the subjectivity of airway appearance alone.

Negative pressure increases microvascular perfusion during severe hemorrhagic shock.

Hemorrhagic shock (HS) is a severe life-threatening condition characterized by loss of blood volume and a lack of oxygen (O2) delivery to tissues. The objective of this study was to examine the impact of manipulating Starling forces in the microcirculation during HS to increase microvascular perfusion without restoring blood volume or increasing O2 carrying capacity. To decrease interstitial tissue pressure, we developed a non-contact system to locally apply negative pressure and manipulate the pressure balance in capillaries, while allowing for visualization of the microcirculation. Golden Syrian hamsters were instrumented with dorsal window chambers and subjected to a controlled hemorrhaged of 50% of the animal's blood volume without any fluid resuscitation. A negative pressure chamber was attached to the dorsal window chamber and a constant negative pressure was applied. Hemodynamic parameters (including microvascular diameter, blood flow, and functional capillary density [FCD]) were measured before and during the four hours following the hemorrhage, with and without applied negative pressure. Blood flow significantly increased in arterioles during negative pressure. The increase in flow through arterioles also improved microvascular perfusion as reflected by increased FCD. These results indicate that negative pressure increases flow in the microcirculation when fluid resuscitation is not available, thus restoring blood flow, oxygen delivery, and preventing the accumulation of metabolic waste. Applying negative pressure might allow for control of microvascular blood flow and oxygen delivery to specific tissue areas.

Purification and analysis of a protein cocktail capable of scavenging cell-free hemoglobin, heme, and iron.

BACKGROUND: Hemolysis releases toxic cell-free hemoglobin (Hb), heme, and iron, which overwhelm their natural scavenging mechanisms during acute or chronic hemolytic conditions. This study describes a novel strategy to purify a protein cocktail containing a comprehensive set of scavenger proteins for potential treatment of hemolysis byproducts. STUDY DESIGN AND METHODS: Tangential flow filtration was used to purify a protein cocktail from Human Cohn Fraction IV (FIV). A series of in vitro assays were performed to characterize composition and biocompatibility. The in vivo potential for hemolysis byproduct mitigation was assessed in a hamster exchange transfusion model using mechanically hemolyzed blood plasma mixed with the protein cocktail or a control colloid (dextran 70 kDa). RESULTS: A basis of 500 g of FIV yielded 62 ± 9 g of a protein mixture at 170 g/L, which bound to approximately 0.6 mM Hb, 1.2 mM heme, and 1.2 mM iron. This protein cocktail was shown to be biocompatible in vitro with red blood cells and platelets and exhibits nonlinear concentration dependence with respect to viscosity and colloidal osmotic pressure. In vivo assessment of the protein cocktail demonstrated higher iron transport to the liver and spleen and less to the kidney and heart with significantly reduced renal and cardiac inflammation markers and lower kidney and hepatic damage compared to a control colloid. DISCUSSION: Taken together, this study provides an effective method for large-scale production of a protein cocktail suitable for comprehensive reduction of hemolysis-induced toxicity.

Safety profile of high molecular weight polymerized hemoglobins.

BACKGROUND: Hemoglobin (Hb)-based oxygen (O2 ) carriers (HBOCs) are being developed as alternatives to red blood cells and blood when these products are unavailable. Clinical trials of previous HBOC generations revealed side effects, including hypertension and vasoconstriction, that were not observed in preclinical studies. Large molecular weight (MW) polymerized bovine Hb (PolybHb) represents a new class of HBOC with promising results. We evaluated the safety profile of PolybHb after an exchange transfusion (ET) in guinea pigs (GPs). This study compares changes in indices of cardiac, inflammatory, and organ function after ET with high (R-state) and low (T-state) O2 affinity PolybHb with high MW. STUDY DESIGN AND METHODS: Guinea pigs underwent a 20% ET with PolybHb. To assess the implication of PolybHb ET on the microcirculation, hamsters instrumented with a dorsal window chamber were subjected to a similar volume ET. RESULTS: T and R-state PolybHb did not induce significant alterations in cardiac function. T-state PolybHb induced mild vasoconstriction shortly after transfusion, while R-state did not have acute effects on microvascular tone. CONCLUSION: Large MW PolybHbs were found to be safe and efficacious in increasing O2 carrying capacity and the O2 affinity of the PolybHb did not affect O2 delivery or extraction by tissues in relevant preclinical models. In conclusion, these results suggest that both T-state and R-state PolybHb are safe and do not impair O2 delivery. The results are encouraging and support further evaluation of high MW PolybHbs and their future feasibility compared to allogenic blood in a trauma model.

Apohemoglobin-haptoglobin complex attenuates the pathobiology of circulating acellular hemoglobin and heme.

Haptoglobin (Hp) is the plasma protein that binds and clears cell-free hemoglobin (Hb), whereas apohemoglobin (apoHb, i.e., Hb devoid of heme) can bind heme. Therefore, the apoHb-Hp protein complex should facilitate holoHb-apoHb αß-dimer exchange and apoHb-heme intercalation. Thus, we hypothesized that apoHb-Hp could facilitate both Hb and heme clearance, which, if not alleviated, could have severe microcirculatory consequences. In this study, we characterized apoHb-Hp and Hb/heme ligand interactions and assessed their in vivo consequences. Hb exchange and heme binding with the apoHb-Hp complex was studied with transfer assays using size-exclusion high-performance liquid chromatography coupled with UV-visible spectrophotometry. Exchange/transfer experiments were conducted in guinea pigs dosed with Hb or heme-albumin followed by a challenge with equimolar amounts of apoHb-Hp. Finally, systemic and microcirculatory parameters were studied in hamsters instrumented with a dorsal window chamber via intravital microscopy. In vitro and in vivo Hb exchange and heme transfer experiments demonstrated proof-of-concept Hb/heme ligand transfer to apoHb-Hp. Dosing with the apoHb-Hp complex reversed Hb- and heme-induced systemic hypertension and microvascular vasoconstriction, reduced microvascular blood flow, and diminished functional capillary density. Therefore, this study highlights the apoHb-Hp complex as a novel therapeutic strategy to attenuate the adverse systemic and microvascular responses to intravascular Hb and heme exposure.NEW & NOTEWORTHY This study highlights the apoHb-Hp complex as a novel therapeutic strategy to attenuate the adverse systemic and microvascular responses to intravascular Hb and heme exposure. In vitro and in vivo Hb exchange and heme transfer experiments demonstrated proof-of-concept Hb/heme ligand transfer to apoHb-Hp. The apoHb-Hp complex reverses Hb- and heme-induced systemic hypertension and microvascular vasoconstriction, preserves microvascular blood flow, and functional capillary density. In summary, the unique properties of the apoHb-Hp complex prevent adverse systemic and microvascular responses to Hb and heme-albumin exposure and introduce a novel therapeutic approach to facilitate simultaneous removal of extracellular Hb and heme.

Robotic surgery and anesthesia for pediatric urologic procedures.

PURPOSE OF REVIEW: Minimally invasive approaches to pediatric surgery have become increasingly popular over the last 15 years. With the advent of robotically controlled instruments, common pediatric urologic surgeries such as pyeloplasty and ureteral reimplantation, which were previously technically challenging, are now commonly performed laparoscopically. It is important to recognize the unique physiologic considerations with this approach and how to provide safe and effective anesthesia for these procedures. RECENT FINDINGS: Although there are multiple studies in the surgical literature describing robot-assisted laparoscopic approaches for pediatric urologic surgery, there are few articles that describe the anesthetic considerations for this type of surgery in children. As the first pediatric hospital in the USA to obtain a surgical robot in 2001, a consistent, collaborative approach has been developed to care for infants and children undergoing robot-assisted laparoscopic surgery. SUMMARY: Robot-assisted laparoscopic surgery is increasingly utilized for common pediatric urologic surgeries. To provide safe and effective anesthesia for this type of surgery, it is important to have a thorough understanding of the multiple physiologic derangements that occur with robot-assisted laparoscopic surgery in infants and children, the potential complications that can occur with this approach and have a consistent approach to the anesthetic management and postoperative pain control for these procedures.

Degree of PEGylatation of Lumbricus terrestris Hemoglobin Improves Microcirculatory Blood Flow but Increases the Rate of Auto-Oxidation.

INTRODUCTION: The demand for red blood cells (RBCs) is on the rise due to the increasing diagnosis of chronic diseases such as sickle cell anemia, malaria, and thalassemia. Despite many commercial attempts, there are no U.S. FDA-approved artificial RBCs for use in humans. Existing RBC substitutes have employed various strategies to transport oxygen, extend the circulation time, and reduce organ toxicity, but none have replicated the natural protective mechanisms of RBCs, which prevent hemoglobin (Hb) dimerization and heme iron oxidation. Lumbricus terrestris (earthworm) erythrocruorin (LtEc) is a naturally occurring extracellular hemoglobin (Hb) with promising attributes: large molecular diameter (30 nm), high molecular weight (3.6 MDa), low auto-oxidation rate, and limited nitric oxide-scavenging properties. These characteristics make LtEc an ideal candidate as an RBC substitute. However, LtEc has a significant drawback, its short circulatory half-life. To address this issue, we explored thiol-mediated surface PEGylation of LtEc (PEG-LtEc) at varying polyethylene glycol (PEG) surface coverages. Increasing PEG surface coverage beyond 40% destabilizes LtEc into smaller subunits that are 1/12th the size of LtEc. Therefore, we evaluated two PEG surface coverage options: PEG-LtEc-0.2 (20% PEGylation) and PEG-LtEc-1.0 (100% PEGylation). METHODS: We conducted experiments using golden Syrian hamsters with dorsal window chambers and catheters to assess the efficacy of these solutions. We measured microvascular parameters, organ function, cerebral blood flow, circulation time, mean arterial pressure, heart rate, and blood gases and performed histology to screen for toxicity. CONCLUSION: Our findings indicate that both PEG-LtEc molecules offer significant benefits in restoring microvascular parameters, organ function, cerebral blood flow, and circulation time compared to LtEc alone. Notably, PEG-LtEc-1.0 showed superior microvascular perfusion, although it exhibited a higher rate of auto-oxidation compared to PEG-LtEc-0.2. These results underscore the advantages of PEGylation in terms of tissue perfusion and organ health while highlighting its limitations.

Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.

Unfortunately, during pathological conditions resulting in chronic hemolysis cell-free hemoglobin (Hb) is released into the circulation that releases free heme, resulting in several complications. One approach to prevent these toxicities is the administration of supplemental scavenger proteins, haptoglobin (Hp) and hemopexin (Hpx). The goal of this body of work is to objectively measure the levels of vascular reactivity and inflammatory profiles after an infusion of acellular hemoglobin in animals that were given a coadministration of PEGylated human apohemoglobin (PEG-apoHb), a hemopexin (Hpx)-mimetic that can scavenge free heme from hemoglobin, together with human plasma-derived Hp that can scavenge dimerized Hb. Using intravital microscopy, Golden Syrian hamsters instrumented with a dorsal window chamber were used to evaluate the in vivo effects of four experimental groups that were then challenged with a hypovolemic injection (10% of the animal's blood volume) of human Hb (hHb, 5 g/dL). The four experimental groups consisted of: 1) lactated Ringer's solution (control), 2) PEG-apoHb only, 3) Hp only, and 4) PEG-apoHb + Hp. The microvascular hemodynamics (diameter and flow) in arterioles and venules were recorded at baseline, 20 min after treatment, and 20 min after hHb challenge. Systemic parameters (blood pressure and heart rate), blood gases (pH, Pco2, and Po2), blood parameters (Hb concentration and hematocrit), and multiorgan functionality/inflammation were also measured. Our results suggest that coadministration of PEG-apoHb + Hp as a booster before the infusion of acellular hemoglobin significantly prevented vasoconstriction in the microcirculation, significantly increased the number of functional capillaries, and significantly reduced inflammation.NEW & NOTEWORTHY Coadministration of PEGylated human apohemoglobin (PEG-apoHb)-a hemopexin (Hpx) mimetic that can scavenge free heme-and human plasma-derived haptoglobin (Hp) that can scavenge hemoglobin (Hb), reduces microcirculatory dysfunction and cardiac and kidney inflammation in a Hb-challenge model.

Toxic side-effects of diaspirin cross-linked human hemoglobin are attenuated by the apohemoglobin-haptoglobin complex.

Alpha-alpha diaspirin-crosslinked human hemoglobin (DCLHb or ααHb) was a promising early generation red blood cell (RBC) substitute. The DCLHb was developed through a collaborative effort between the United States Army and Baxter Healthcare. The core design feature underlying its development was chemical stabilization of the tetrameric structure of hemoglobin (Hb) to prevent Hb intravascular dimerization and extravasation. DCLHb was developed to resuscitate warfighters on the battlefield, who suffered from life-threatening blood loss. However, extensive research revealed toxic side effects associated with the use of DCLHb that contributed to high mortality rates in clinical trials. This study explores whether scavenging Hb and heme via the apohemoglobin-haptoglobin (apoHb-Hp) complex can reduce DCLHb associated toxicity. Awake Golden Syrian hamsters were equipped with a window chamber model to characterize the microcirculation. Each group was first infused with either Lactated Ringer's or apoHb-Hp followed by a hypovolemic infusion of 10% of the animal's blood volume of DCLHb. Our results indicated that animals pretreated with apoHb-Hb exhibited improved microhemodynamics vs the group pretreated with Lactated Ringer's. While systemic acute inflammation was observed regardless of the treatment group, apoHb-Hp pretreatment lessened those effects with a marked reduction in IL-6 levels in the heart and kidneys compared to the control group. Taken together, this study demonstrated that utilizing a Hb and heme scavenger protein complex significantly reduces the microvasculature effects of ααHb, paving the way for improved HBOC formulations. Future apoHb-Hp dose optimization studies may identify a dose that can completely neutralize DCLHb toxicity.

Focal drug-resistant temporal lobe epilepsy associated with an ipsilateral anterior choroidal artery aneurysm: illustrative case.

BACKGROUND: The occurrence of both an intracranial aneurysm and epilepsy, especially drug-resistant epilepsy (DRE), is rare. Although the overall incidence of aneurysms associated with DRE is unclear, it is thought to be particularly infrequent in the pediatric population. Surgical ligation of the offending aneurysm has been reported in conjunction with resolving seizure activity, although few cases have cited a combined approach of aneurysm ligation and resection of an epileptogenic focus. OBSERVATIONS: We present the case of a 14-year-old female patient with drug-resistant temporal lobe epilepsy and an ipsilateral supraclinoid internal carotid artery aneurysm. Seizure semiology, electroencephalography monitoring, and magnetic resonance imaging all indicated a left temporal epileptogenic focus, in addition to an incidental aneurysm. The authors recommended a combined surgery involving resection of the temporal lesion and surgical clip ligation of the aneurysm. Near-total resection and successful ligation were achieved, and the patient has remained seizure free since surgery at 1 year postoperatively. LESSONS: In patients with focal DRE and an adjacent intracranial aneurysm, a combined surgical approach involving both resection and surgical ligation can be used. Several surgical timing and neuroanesthetic considerations should be made to ensure the overall safety and efficacy of this procedure.

Implications of microvascular dysfunction and nitric oxide mediated inflammation in severe COVID-19 infection.

Infection with COVID-19 has resulted in over 276,000 deaths in the United States and over 1.5 million deaths globally, with upwards of 15% of patients requiring hospitalization. Severe COVID-19 infection is, in essence, a microvascular disease. This contention has been emphasized throughout the course of the pandemic, particularly due to the clinical manifestation of severe infection. In fact, it has been hypothesized and shown in particular instances that microvascular function is a significant prognosticator for morbidity and mortality. Initially thought to be isolated to the pulmonary system and resulting in ARDS, patients with COVID-19 have been observed to have acute cardiac, renal, and thrombolytic complications. Therefore, severe COVID-19 is a vascular disease that has systemic implications. The objective of this review is to provide a mechanistic background for the microvascular nature of severe COVID-19 infection, with a particular emphasis on dysfunction of the endothelial glycocalyx and nitric oxide mediated pathogenesis.

Apohemoglobin-haptoglobin complex alleviates iron toxicity in mice with ß-thalassemia via scavenging of cell-free hemoglobin and heme.

ß-thalassemia is a genetic hemoglobin (Hb) disorder that affects millions of people world-wide. It is characterized by ineffective erythropoiesis and anemia. The resultant chronic anemia can require life-long blood transfusion regimens, leading to secondary hemochromatosis. Moreover, the abnormal red blood cells (RBCs) from ß-thalassemia patients are prone to hemolytic events that release cell-free Hb and heme causing a series of events that result in oxidative organ and tissue damage. In this study, ß-thalassemic mice were treated with a protein scavenger for six weeks, apohemoglobin-haptoglobin (apoHb-Hp), this protein scavenges cell free Hb and heme. We hypothesize that scavenging cell-free Hb and heme will lead to a positive therapeutic event. After the apoHb-hp treatment it was observed to reduce the weight of the liver and spleen and show an improvement in liver function by a drop in ALT, AST, and ALP markers. ApoHb-hp treatment also hints at an improved RBC half-life as the number of reticulocytes decreased, the mean corpuscular volume (MCV) increased, mean corpuscular hemoglobin increase and the RBC distribution width decreased. Furthermore, apoHb-Hp treatment reduced circulating serum iron concentration and transferrin saturation concentration. Based on these outcomes, introducing a scavenger protein can benefit ß-thalassemic mice. This study demonstrated that apoHb-Hp treatment may be a viable strategy to mitigate toxicities associated with cell free Hb and heme, a driver of ß-thalassemic issues.

Attenuating ischemia-reperfusion injury with polymerized albumin.

Ischemia-reperfusion injury increased vascular permeability, resulting in fluid extravasation from the intravascular compartment into the tissue space. Fluid and small protein extravasation lead to increased interstitial fluid pressure and capillary collapse, impairing capillary exchange. Polymerized human serum albumin (PolyHSA) has an increased molecular weight (MW) compared with unpolymerized human serum albumin (HSA) and can improve intravascular fluid retention and recovery from ischemia-reperfusion injury. To test the hypothesis that polymerization of HSA can improve recovery from ischemia-reperfusion injury, we studied how exchange transfusion of 20% of the blood volume with HSA or PolyHSA immediately before reperfusion can affect local ischemic tissue microhemodynamics, vascular integrity, and tissue viability in a hamster dorsal window chamber model. Microvascular flow and functional capillary density were maintained in animals exchanged with PolyHSA compared with HSA. Likewise, exchange transfusion with PolyHSA preserved vascular permeability measured with extravasation of fluorescently labeled dextran. The intravascular retention time of the exchanged PolyHSA was significantly longer compared with the intravascular retention time of HSA. Lastly, the viability of tissue subjected to ischemia-reperfusion injury increased in animals exchanged with PolyHSA compared with HSA. Therefore maintenance of microvascular perfusion, improvement in vascular integrity, and reduction in tissue damage resulting from reperfusion with PolyHSA suggest that PolyHSA is a promising fluid therapy to improve outcomes of ischemia-reperfusion injury.NEW & NOTEWORTHY Polymerized human serum albumin reduced reperfusion injury and preservers microvascular hemodynamics. Polymerized human serum albumin reduces fluid extravasation and prevents fluid extravasation. Consequently, the tissue viability of ischemic tissue is preserved by polymerized human serum.

Application of negative tissue interstitial pressure improves functional capillary density after hemorrhagic shock in the absence of volume resuscitation.

Microvascular fluid exchange is primarily dependent on Starling forces and both the active and passive myogenic response of arterioles and post-capillary venules. Arterioles are classically considered resistance vessels, while venules are considered capacitance vessels with high distensibility and low tonic sympathetic stimulation at rest. However, few studies have investigated the effects of modulating interstitial hydrostatic pressure, particularly in the context of hemorrhagic shock. The objective of this study was to investigate the mechanics of arterioles and functional capillary density (FCD) during application of negative tissue interstitial pressure after 40% total blood volume hemorrhagic shock. In this study, we characterized systemic and microcirculatory hemodynamic parameters, including FCD, in hamsters instrumented with a dorsal window chamber and a custom-designed negative pressure application device via intravital microscopy. In large arterioles, application of negative pressure after hemorrhagic shock resulted in a 13 ± 11% decrease in flow compared with only a 7 ± 9% decrease in flow after hemorrhagic shock alone after 90 minutes. In post-capillary venules, however, application of negative pressure after hemorrhagic shock resulted in a 31 ± 4% decrease in flow compared with only an 8 ± 5% decrease in flow after hemorrhagic shock alone after 90 minutes. Normalized FCD was observed to significantly improve after application of negative pressure after hemorrhagic shock (0.66 ± 0.02) compared to hemorrhagic shock without application of negative pressure (0.50 ± 0.04). Our study demonstrates that application of negative pressure acutely improves FCD during hemorrhagic shock, though it does not normalize FCD. These results suggest that by increasing the hydrostatic pressure gradient between the microvasculature and interstitium, microvascular perfusion can be transiently restored in the absence of volume resuscitation. This study has significant clinical implications, particularly in negative pressure wound therapy, and offers an alternative mechanism to improve microvascular perfusion during hypovolemic shock.

A Review on Microvascular Hemodynamics: The Control of Blood Flow Distribution and Tissue Oxygenation.

The microcirculation is a complex network of vessels ranging from as large as 100 µm to as small as 5 µm. This complex network is responsible for the regulation of oxygen to the surrounding tissues and ensures metabolite washout. With a more complete understanding of the microcirculation's physiologic and pathologic tendencies, engineers can create new solutions to combat blood pathologies and shock-related diseases. Over the last number of decades a grown interest in the microcirculation has resulted in the development of fundamental techniques to quantify the microvasculature flow and the release of oxygen to tissues.

Enhanced Photodynamic Therapy Using the Apohemoglobin-Haptoglobin Complex as a Carrier of Aluminum Phthalocyanine.

Photodynamic therapy (PDT) has been shown to effectively treat cancer by producing cytotoxic reactive oxygen species via excitation of photosensitizer (PS). However, most PS lack tumor cell specificity, possess poor aqueous solubility, and cause systemic photosensitivity. Removing heme from hemoglobin (Hb) yields an apoprotein called apohemoglobin (apoHb) with a vacant heme-binding pocket that can efficiently bind to hydrophobic molecules such as PS. In this study, the PS aluminum phthalocyanine (Al-PC) was bound to the apoHb-haptoglobin (apoHb-Hp) protein complex, forming an apoHb-Al-PC-Hp (APH) complex. The reaction of Al-PC with apoHb prevented Al-PC aggregation in aqueous solution, retaining the characteristic spectral properties of Al-PC. The stability of apoHb-Al-PC was enhanced via binding with Hp to form the APH complex, which allowed for repeated Al-PC additions to maximize Al-PC encapsulation. The final APH product had 65% of the active heme-binding sites of apoHb bound to Al-PC and a hydrodynamic diameter of 18 nm that could potentially reduce extravasation of the molecule through the blood vessel wall and prevent kidney accumulation of Al-PC. Furthermore, more than 80% of APH's absorbance spectra were retained when incubated for over a day in plasma at 37 °C. Heme displacement assays confirmed that Al-PC was bound within the heme-binding pocket of apoHb and binding specificity was demonstrated by ineffective Al-PC binding to human serum albumin, Hp, or Hb. In vitro studies confirmed enhanced singlet oxygen generation of APH over Al-PC in aqueous solution and demonstrated effective PDT on human and murine cancer cells. Taken together, this study provides a method to produce APH for enhanced PDT via improved PS solubility and potential targeted therapy via uptake by CD163+ macrophages and monocytes in the tumor (i.e., tumor-associated macrophages). Moreover, this scalable method for site-specific encapsulation of Al-PC into apoHb and apoHb-Hp may be used for other hydrophobic therapeutic agents.